Cobalt carbonyl-mediated carbocyclizations of enynes: Generation of bicyclooctanones or monocyclic alkenes

Article abstract of DOI:10.1021/jo016118v

Depending on the thermolytic conditions, dicobalthexacarbonyl-complexed enynes underwent cyclizations to provide different carbocyclic frameworks. Bicyclopentanones were formed from enyne-Co₂(CO)₆ complexes, or from enynes that were treated with Co₂(CO)₈, or more effectively, with Co₄(CO)₁₂ in an alcoholic solvent under a H₂ or N₂ atmosphere. This transformation proceeded via a sequential cyclocarbonylation and 1,4-reduction and is the first account using the cobalt carbonyl cluster. Under these conditions a cobalt hydride was presumably generated, which mediated reduction of the enone to the saturated ketone. In contrast, thermolysis of dicobalthexacarbonyl-complexed enynes under a hydrogen atmosphere in toluene resulted in their reductive cyclization to form monocyclic alkenes in moderate yields, in addition to the bicyclopentenone product. In some cases, addition of a hydrosilane to the reaction induced a complete suppression of the bicyclopentenone formation. While the former results demonstrate a reaction that occurs after the cycloaddition, the latter depicts another example of an interruption of the normal route in the Pauson-Khand reaction pathway.

Full text of DOI:10.1021/jo016118v

J . Org. Chem. 2002, 67, 1233-1246
1233
Coba lt Ca r bon yl-Med ia ted Ca r bocycliza tion s of En yn es:
Gen er a tion of Bicycloocta n on es or Mon ocyclic Alk en es
Marie E. Krafft,* Llorente Vicente R. Bo n˜ aga, J ames A. Wright, and Chitaru Hirosawa
Department of Chemistry and Biochemistry, The Florida State University,
Tallahassee, Florida 32306-4390
mek@chem.fsu.edu
Received September 14, 2001
Depending on the thermolytic conditions, dicobalthexacarbonyl-complexed enynes underwent
cyclizations to provide different carbocyclic frameworks. Bicyclopentanones were formed from
enyne-Co
2
(CO)
6
complexes, or from enynes that were treated with Co
2 8
(CO) , or more effectively,
with Co (CO)12 in an alcoholic solvent under a H
4
2
or N atmosphere. This transformation proceeded
2
via a sequential cyclocarbonylation and 1,4-reduction and is the first account using the cobalt
carbonyl cluster. Under these conditions a cobalt hydride was presumably generated, which
mediated reduction of the enone to the saturated ketone. In contrast, thermolysis of dicobalth-
exacarbonyl-complexed enynes under a hydrogen atmosphere in toluene resulted in their reductive
cyclization to form monocyclic alkenes in moderate yields, in addition to the bicyclopentenone
product. In some cases, addition of a hydrosilane to the reaction induced a complete suppression of
the bicyclopentenone formation. While the former results demonstrate a reaction that occurs after
the cycloaddition, the latter depicts another example of an interruption of the normal route in the
Pauson-Khand reaction pathway.
In tr od u ction
6
(CO) complexes that were derived from 1-(1-alkynyl)-
cyclopropanols have been also reported to rearrange to
Highly complex structural motifs have frequently been
assembled via an organometallic approach using a tran-
sition metal as a template for preorganizing typically
simple reactive groups. Not surprisingly, this extremely
successful approach continues to be a focus of many
research groups. In the quest to understand more fully
the mechanism of these reactions new and more elaborate
transformations have been discovered.
Cobalt-based organic processes is one of the widely
explored arenas in the vast array of reactions based on
transition metals.1g Specifically, cobalt complexes are
instrumental in promoting different reactivity patterns
of alkynes with other unsaturated moieties.1h As a class
of low-valent organometallic compounds, dicobalthexa-
carbonyl complexed alkynes, are commonly used as (a) a
5a
2
-cyclopenten-1-ones. And most recently, an appropri-
ately substituted (phenylthio)acetylene-cobalt carbonyl
complex was shown to undergo an oxidative intramo-
5b
lecular [4 + 2] cycloaddition.
In the same vein, it was also shown in our laboratories
that under the appropriate reaction conditions, other
carbocyclic frameworks could likewise be generated from
reactions of dicobalthexacarbonyl-complexed enynes. For
instance, 1,3-dienes were formed in good yields from
the thermolysis of dicobalthexacarbonyl complexes of
1
6
unactivated 1,6- and 1,7-enynes (Scheme 1). Interest-
ingly, instead of the anticipated bicyclic enones, mono-
cyclic enones were, in most cases, formed exclusively from
the thermolyses of these complexes under an oxygenated
atmosphere (air, 5% oxygen in nitrogen, or pure oxygen)
component in the Pauson-Khand reaction (PKR) to give
Scheme 1).7 Meanwhile, thermolysis of the dicobalt-
(
2
2
-cyclopenten-1-ones upon reaction with alkenes, (b) a
hexacarbonyl complex of 1-trimethylsilyl-6-hepten-1-ynes
under an argon atmosphere was most recently noted by
3
protective group for alkynyl functionality, and (c) a
stabilizing moiety for propargylic cations in nucleophilic
8
Gleason to generate vinyl cyclopentenes. Formation of
4
substitution reactions (Nicholas reaction). Alkyne-Co
2
-
(
3) Melikyan, G. G.; Vostrowsky, O.; Bauer, W.; Bestmann, H. J .;
(
1) (a) J acobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. Comprehen-
sive Asymmetric Catalysis; Springer-Verlag: Berlin, 1999; Vols. 1 and
. (b) Beller, M., Bolm, C., Eds. Transition Metals in Organic Synthesis;
Khan, M.; Nicholas, K. M. J . Org. Chem. 1994, 59, 222. Milgrom, L.
R.; Rees, R. D.; Yahioglu, G. Tetrahedron Lett. 1997, 38, 4905.
(4) Caffyn, A. J .; Nicholas, K. M. In Comprehensive Organometallic
Chemistry II, Vol. 12; Abel, E. W., Stone, F. A., Wilkinson, G., Eds.;
Elsevier: New York, 1995; p 685. Caddick, S.; Delisser, V. M.
Tetrahedron Lett. 1997, 38, 2355.
(5) (a) Iwasawa, N.; Matsuo, T.; Iwamoto, T.; Ikeno, T. J . Am. Chem.
Soc. 1998, 120, 3903. Iwasawa, N. Synlett 1999, 13. (b) Kita, Y.; Iio,
K.; Kawaguchi, K.; Fukuda, N.; Takeda, Y.; Ueno, H.; Okunaka, R.;
Higuchi, K.; Tsujino, T.; Fujioka, H.; Akai, S. Chem. Eur. J . 2000, 6,
3897.
(6) Krafft, M. E.; Wilson, A. M.; Dasse, O. A.; Bo n˜ aga, L. V. R.;
Cheung, Y. Y.; Fu, Z.; Shao, B.; Scott I. L. Tetrahedron Lett. 1998, 39,
5911.
(7) Krafft, M. E.; Wilson, A. M.; Dasse, O. A.; Shao, B.; Chung, Y.
Y.; Fu, Z.; Bo n˜ aga, L. V. R.; Mollman, M. K. J . Am. Chem. Soc. 1996,
118, 6080.
2
Wiley-VCH: Weinhem, 1998; Vol. 1 and 2. (c) Fruhauf, H.-W. Chem.
Rev. 1997, 97, 523. (d) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan,
R. J . Chem. Rev. 1996, 96, 635. (e) Lautens, M.; Klute, W.; Tam, W.
Chem. Rev. 1996, 96, 49. (f) An entire issue of Chem. Rev. was devoted
to the utility of organometallics in organic synthesis: Chem. Rev. 2000,
00, 2739-3282. (g) For a recent review of organocobalt complexes in
organic synthesis, see: Welker, M. E. Curr. Org. Chem. 2001, 5, 785.
h) For enyne cycloisomerizations mediated by Co(I) complexes, see:
Buisine, O.; Aubert, C.; Malacria, M. Chem. Eur. J . 2001, 7, 3517.
1
(
(
2) For leading references on the Pauson-Khand reaction, see (a)
Brummond, K. M.; Kent, J . L. Tetrahedron 2000, 56, 3263. (b) Schore,
N. E. In Comprehensive Organometallic Chemistry II, Vol. 12; Abel,
E. W., Stone, F. A., Wilkinson, G., Eds.; Elsevier: New York, 1995; p
7
03.
1
0.1021/jo016118v CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/30/2002

1
234 J . Org. Chem., Vol. 67, No. 4, 2002
Krafft et al.
Sch em e 1
cyclopentanones had been frequently encountered as
1
4
trace byproducts in their earlier cyclization studies. To
date only three studies that exploited the exclusive
formation of saturated ketones are available (Table 1).
In a detailed study on PK cyclizations of N-acyl allyl
propargylamines, exclusive formation of cyclopentanones
was achieved by Pauson using several protocols (entry
1
4
1
). In these studies, related complexes of 1,7-enynes
underwent the normal Pauson-Khand cyclization re-
gardless of the reaction conditions. A systematic study
was also conducted by Becker that demonstrated the
exclusive formation of azabicyclic saturated ketones from
enynes.15 Pauson-Khand reactions under the Smit-
Caple DSAC (dry state adsorption conditions) protocol
in an inert atmosphere provided excellent yields of aza-
bicyclo[3.3.0]octanones from N-protected allyl propargyl-
amines. Standard cyclizations in air gave mixtures of
ketones and enones (entry 2). The reversal of the reaction
course is noteworthy in cyclizations of benzylated sub-
other products, such as arenes, cyclopropyl ketones, and
other ketonic products has also been known but has
received less attention.9 These interrupted Pauson-
Khand reactions have resulted from a modification of
reaction conditions, which has changed the normal
Pauson-Khand reaction pathway, and have led to
the formation of other carbocyclic frameworks. Herein,
we disclose findings from our most recent studies on
the carbocyclizations of enynes, via their dicobalt-
hexacarbonyl-complexed alkyne complexes, that result
in the generation of bicyclo[3.3.0]octanones (reductive
Pauson-Khand reaction) or monocyclic alkenes (reductive
cyclization) (Scheme 1).
2
strates under a N atmosphere and air. This protocol was
subsequently applied to the construction of the key meso-
azabicyclo[3.3.0] intermediate for the syntheses of the
antagonists SC-52490 and SC-52491 via the enantiomeric
15c
azanoadamantane. It was also reported by Periasamy
that in the presence of trifluoroacetic acid, cyclopen-
tanones were formed from the Pauson-Khand reactions
of cobalt alkyne complexes with norbornene under a CO
atmosphere although minor amounts of cyclopentenones
16
were still observed (entry 3). Under these reaction
conditions, a cobalt carbonyl complex was generated in
situ from the reduction of CoBr by Zn metal, which then
2
underwent reaction with the alkyne.
4
During our studies to explore the reactivity of Co -
Resu lts a n d Discu ssion
1
7
(
CO)12
,
in particular with enynes, we discovered that
reaction of enyne 1 with a stoichiometric amount of Co
CO)12 in 2-propanol under a H atmosphere provided a
A. Bicyclo[3.3.0]octa n on e F or m a tion : Red u ctive
P a u son -Kh a n d Rea ction of En yn es. Unlike the PKR,
the analogous formation of cyclopentanones from alkenes
and alkynes, the reductive PKR, has been studied less
frequently. With the exception of a handful of detailed
studies, only sporadic reports are available which de-
scribe cyclopentanone formation as a side reaction in
several modified Pauson-Khand reaction procedures.10
Unless the enone moiety formed from the PKR is needed
for further elaboration, this protocol is a very straight-
forward approach to the bicyclo[3.3.0]octanone frame-
work from enynes. This structure appears as a core
4
-
(
2
good yield of a cyclopentanone 2 (eq 1). A reductive
Pauson-Khand cyclization of enynes had presumably
occurred under these conditions. It is in fact documented
that Co
4 2 8
(CO)12 could be transformed into Co (CO) in
2
(
-propanol under a CO atmosphere at room temperature
18,19
eq 2).
Dicobaltoctacarbonyl is widely used as the
source of cobalt carbonyl to form dicobalthexacarbonyl
(12) For examples: (-)-R-kainic acid: Yoo, S.; Lee, S. H. J . Org.
Chem. 1994, 59, 6968. Pentalenenes: Schore, N. E.; Rowley, E. G. J .
Am. Chem. Soc. 1988, 110, 5224. pentalenic acid: Rowley, E. G.;
Schore, N. E. J . Organomet. Chem. 1991, 413,C5. silphinine tri-
quinanes: Rowley, E. G.; Schore, N. E. J . Org. Chem. 1992, 57, 6853.
C/D diquinane substructure of kalmanol: Paquette, L. A.; Borrelly, S.
J . Org. Chem. 1995, 60, 6912. Dendrobine: Cassayre, J .; Zard, A. Z.
J . Organomet. Chem. 2001, 64, 316. Cassayre, J .; Zard, A. Z. J . Am.
Chem. Soc. 1999, 121, 6072. spatane nucleus: Dauben, W. G.;
Kowalczyk, B. A. Tetrahedron Lett. 1990, 31, 635. Kowalczyk, B. A.;
Smith, T. C.; Dauben, W. G. J . Org. Chem. 1998, 63, 1379. 9-cis-
Retinoic acid: Murray, A.; Hansen, J . B.; Christensen, B. V. Tetra-
hedron Lett. 2001, 571, 7383.
skeleton in many natural products, such as the linearly
and angularly fused triquinane sesquiterpenes.11 Key
steps in several synthetic studies and total syntheses
have been based on a stepwise PK cyclization and
subsequent 1,4-reduction.12
Isolation and identification of cyclopentanones under
the PKR conditions at unusually high temperatures were
first accounted by Serratosa.13 Pauson later reported that
(
13) Almansa, C.; Carceller, E.; Garcia, M. L.; Torrents, A.; Serra-
(
(
8) Dolaine, R.; Gleason, J . L. Org. Lett. 2000, 2, 1753.
9) Borodkin, V. S.; Shpiro, N. A.; Azov, V. A.; Kochetkov, N. K.
tosa, F. Synth. Commun. 1988, 18, 381. Almansa, C.; Carceller, E.;
Garcia, M. L.; Serratosa, F. Synth. Commun. 1988, 18, 1079. Monta n˜ a,
A.-M.; Moyano, A.; Peric a` s, M. A.; Serratosa, F. Tetrahedron 1985, 41,
5995. Montana, A.-M.; Moyano, A.; Pericas, M. A.; Serratosa, F. Ann.
Quim. 1988, 84, 82.
Tetrahedron Lett. 1996, 37, 1489. Kagoshima, H.; Hayashi, M.;
Hashimoto, Y.; Saigo, K. Organometallics 1996, 15, 5439. Schore, N.
E.; Croudace, M. C. J . Org. Chem. 1981, 46, 5436.
(
10) (a) J eong, N.; Chung, Y. K.; Lee, B. Y.; Lee, S. H.; Yoo, S. Synlett
(14) Brown, S. W.; Pauson, P. L. J . Chem. Soc., Perkin Trans. 1 1990,
1205.
1
991, 204. (b) J eong, N.; Yoo, S.; Lee, S. J .; Lee, S. H.; Chung, Y. K.
Tetrahedron Lett. 1991, 32, 2137. (c) Chung, Y. K.; Lee, B. Y.; J eong,
N.; Hudecek, M.; Pauson, P. L. Organometallics 1993, 12, 220. (d)
Ma n˜ as, M. N.; Pleixats, R.; Roglans, A. Liebigs Ann. 1995, 1807.
(15) (a) Becker, D. P.; Flynn, D. L. Tetrahedron Lett. 1993, 34, 2087.
(b) Becker, D. P.; Flynn, D. L. Tetrahedron 1993, 49, 5047. (c) Becker,
D. P.; Nosal, R.; Zabrowski, D. L.; Flynn, D. L. Tetrahedron 1997, 53, 1.
(16) Rao, M. L. N.; Periasamy, M. J . Organomet. Chem. 1997, 532,
143.
(17) Krafft, M. E.; Bo n˜ aga, L. V. R. Angew. Chem., Int. Ed. 2000,
39, 3676.
(11) (a) Paquette, L. A.; Doherty, A. M. Polyquinane Chemistry:
Reactivity and Structure; Concepts in Organic Chemistry; Springer-
Verlag: New York, 1987; Vol. 26. (b) Fraga, B. M Nat. Prod. Rep. 1992,
9
, 217. (c) Hanson, J . R. Nat. Prod. Rep. 1992, 9, 481. See ref 2 for
reviews of applications of the PKR in natural product synthesis.
(18) Chini, P.; Heaton, B. T. Top. Curr. Chem. 1977, 71, 3.

Cobalt Carbonyl-Mediated Carbocyclizations
J . Org. Chem., Vol. 67, No. 4, 2002 1235
Ta ble 1. Accou n ts of th e System a tic Stu d ies on th e Red u ctive P a u son -Kh a n d Rea ction
Ta ble 2. P r elim in a r y Stu d ies on th e Red u ctive
complexes with alkynes under stoichiometric and cata-
lytic conditions.2,20 Unless the enone moiety is needed for
a
P a u son -Kh a n d Rea ction of En yn es
elaboration, this transformation should be potentially
synthetically useful. Thus, we set out to investigate the
scope and mechanism of this interesting reaction.
% yield
Co4(CO)12
(no. of equiv)
reaction
atmosphere
entry
1
substrate
3
2
1
1
1
1
1
1
1
1
1
1
1
1
0.35
0.25
0.50
0.50
0.20
1
H2
H2
H2
N2
H2
H2/CO
H2
N2
H2
H2
N2
H2
N2
-
-
67
65
56
56
17
8
81
44
40
74
71
81
91
b
2
3
c
-
4
5
6
7
8
9
0
1
2
3
-
42
65
7
11
41
-
3
3
3
1
1
1
1
1
1
1
-
P r elim in a r y Stu d ies. We initiated our studies by
generating ketone 2 independently. Catalytic hydrogena-
tion of enone 3, the Pauson-Khand cycloadduct of enyne
d
e
3 + 4
3 + 4
-
-
a
Reactions were carried out at a substrate concentration of
1
, provided an 89% yield of the saturated ketone 2 (0.03
M EtOH, catalytic Pd/C, H ). We further investigated the
origin of these unprecedented observations using Co
CO)12, which subsequently led us to finding optimal
b
0
.005 M, unless specified otherwise, in i-PrOH at 70 °C. 0.05 M.
c
.10 M. d 73% 5. e 78% 5.
2
0
4
-
(
conditions for the reaction (Table 2). To determine
whether the observed transformation was a consequence
of high dilution, reactions were carried out using different
concentrations. The results indicated no significant change
as a function of dilution (entries 1-3). Complete conver-
sion of enyne 1 to bicyclopentanone 2 could be effected
using a stoichiometric amount of Co
atmosphere (entry 1) although a slightly better yield of
was observed when using only 50 mol % of Co
entry 7). Using 25 or 35 mol % of Co (CO)12 led to the
isolation of mixtures of enone 3 and ketone 2 (entries 5
and 6).
In our attempts to improve the yield using less than 1
4 2
equiv of Co (CO)12, a mixture of H and CO was used with
the hope of regenerating and/or preserving the cobalt
carbonyl complexes, which promote the desired trans-
4 2
(CO)12 under a H
formations.19 Unfortunately, no improvement was ob-
served as is evident by the result in entry 6. Furthermore,
reaction of enyne 1 furnished the bicyclopentanone in
2
(
4
(CO)12
4
good yield under a N
yield than the reaction under a H
vs 4). Contrary to our initial assumption that H
reducing agent, this result suggests that the transforma-
tion does not require a H atmosphere.
Interestingly, reaction of enone 3 with 1 equiv of Co
CO)12 under an atmosphere of either H or N yielded
2
atmosphere, albeit in slightly lower
atmosphere (entry 1
was the
2
2
2
4
-
(
2
2
ketone 2 in good yields (entries 9 vs 10 and 11). In
addition, reactions of a mixture of enone 3 and enyne 4
with Co (CO)12 under a N or H atmosphere gave similar
4 2 2
yields of bicyclopentanone 5 (entries 12 and 13). Forma-
tion of the corresponding bicyclopentanones in good yields
(
19) Catalytic Pauson-Khand reactions are carried out under a
CO atmosphere to regenerate the active cobalt carbonyl complex. See
ref 2.
(
20) For references on cyclizations of these enynes using catalytic
amounts of Co (CO) , see Krafft, M. E.; Bo n˜ aga, L. V. R.; Hirosawa,
C. J . Org. Chem. 2001, 66, 3004.
2
8

1
236 J . Org. Chem., Vol. 67, No. 4, 2002
Krafft et al.
Ta ble 3. Red u ctive P a u son -Kh a n d Rea ction s of En yn es Usin g Co4(CO)12 in i-P r OHa
a
Reactions were carried out at substrate concentrations of 0.005 M in 2-propanol using 1 equiv of Co4(CO)12, unless specified otherwise,
under a H2 atmosphere at 70 °C. Reactions were typically complete in 15-18 h. b 0.5 equiv of Co4(CO)12.
from a mixture of enyne 4 and bicyclopentenone 3 (entries
2 and 13) or from enone 3 (entry 10) alone suggested
that the cobalt carbonyl species generated under these
reaction conditions promoted both enyne cyclocarbonyl-
ation and enone reduction processes under a N atmo-
2
sphere. Thus, our preliminary studies indicated that
reductive PK reactions could be best achieved using
of the reaction. Disubstitution on the alkyne component
1
of the 1,6-enynes provided solely the Pauson-Khand
cycloadducts albeit in moderate yields (entries 8-10).
This failure of the tetrasubstituted enones to undergo
further 1,4-reduction has been independently reported
1
4-16
in the early studies by several research groups.
It
should be noted however, that only under the DSAC
procedure developed by Becker were saturated ketones
formed in significant amounts.15 No saturated ketones
were observed under our conditions as in the procedures
reported by Pauson14 and Periasamy when internal
alkynes were used as substrates. Disubstitution, how-
ever, in both the reactive unsaturated groups in a 1,6-
enyne furnished a monocyclic alkene along with the usual
bicyclic enone (entry 11).
stoichiometric or substoichiometric amounts of Co
4
(CO)12
in 2-propanol at 70 °C under a H atmosphere.
2
Scop e of th e Rea ction . The scope and limitations of
these observations are evident in the examples depicted
in Table 3. As shown, good yields of the saturated
carbocyclic and heterocyclic ketones were obtained from
16
1
,6-enynes bearing a terminal alkyne (entries 1-7). Use
of less than 1 equiv of Co (CO)12 led to the formation of
4
minor amounts of enone 23 from enyne 10 (entry 7) due
to the incomplete conversion of the enone to the saturated
ketone. Unlike substitution on the alkyne moiety (vide
infra), disubstitution in the alkene did not affect the fate
On the contrary, reactions of 1,7-enynes yielded no
saturated ketones (entries 12 and 13). In this case,
monocyclic alkenes, in addition to the corresponding
Pauson-Khand cycloadducts, were formed. In the studies

Cobalt Carbonyl-Mediated Carbocyclizations
J . Org. Chem., Vol. 67, No. 4, 2002 1237
Ta ble 4. Cycliza tion s in 2-P r op a n ol w ith Differ en t
Coba lt Ca r bon yl Sou r ces a n d Rea ction Atm osp h er es
Ta ble 5. Solven t Effect on Co4(CO)12-Med ia ted
Cycliza tion s u n d er a Nitr ogen Atm osp h er e
%
yield
entry
solvent
methanol
ethanol
2-propanol
time (h)a
3
2
1
2
3
4
5
6
23.5
16
15
25
33
-
25
-
69
53
60
17
44
38
56
6
-
-
-
-
-
%
yield
nitrogen
hydrogen
carbon monoxide
cobalt carbonyl
source
tert-butyl alcohol
24
3
2
3
2
3
2
dimethyl sulfoxideb
13.5
21.5
21.5
21.5
16
acetonitrile
Co
Co
enyne-Co
4
(CO)12
(CO)
-
7
38
56
48
60
-
58
7
67
21
67
49
41
15
47
17
52
c
7
8
2
8
d
(CO) a
2
6
9
dichloroethane
a
Isolated cobalt carbonyl complex of enyne 1.
a
In all cases the enyne was completely consumed within 1 h,
as determined by TLC. 72% recovered enyne. c H2 atmosphere,
N2 atmosphere, 5 equiv of i-PrOH.
b
conducted by Pauson, reaction of N-acetyl-N-allyl-N-but-
-ynylamine provided only the corresponding bicyclopen-
tenone under various reaction conditions (isooctane at
00 °C, 50 °C under UV light, or 60 °C under ultrasound,
and the DSAC procedure). Under the present reaction
conditions we also noted significant formation of mono-
cyclic alkenes, in addition to the normal Pauson-Khand
reaction adduct, from reactions of 1,6-enynes bearing a
disubstituted alkene and 1,7-enynes.
d
3
though a H
these reactions, cyclizations of enyne 1 in different
solvents were conducted under a N atmosphere to
2
atmosphere was apparently beneficial to
1
1
4
2
ascertain the origin of the hydrogen atoms incorporated
in the saturated ketone (Table 5). As shown, enone
reduction was only observed in alcoholic solvents, where
the highest efficiency was achieved in 2-propanol (entries
The hydrogenolysis observed in the cycloadducts de-
rived from the substrates bearing a silylated allylic
alcohol (entry 6) and a propargylated ether (entry 10)
1
-4 vs entries 5-9). A mixture of 3 and 2 was obtained
from reactions conducted in primary and tertiary alco-
holic solvents (entries 1, 2, and 4). Cyclizations in aprotic
solvents did not provide the desired transformation but
gave only the Pauson-Khand cycloadducts. Reaction in
dimethyl sulfoxide (DMSO) only furnished the starting
enyne 1 (entry 5). It had been observed in our studies on
deserves comments. Silylated allylic alcohols are typically
stable under the Pauson-Khand reaction conditions.20,21
However, under the protic reaction conditions, elimina-
tion of the silyl ether â to the ketone (entry 6) should be
a facile process, and subsequent reduction of the resulting
enone would necessarily follow. Hydrogenolysis of ether
linkages in bicyclopentenone adducts has been observed
4
the catalytic Pauson-Khand reaction using Co (CO)12
under a CO atmosphere that use of DMSO as the solvent
by J eong1 and others and was believed to occur as a
result of formation of a hydrido cobalt complex. Finally,
as shown in entry 7, transesterification might also occur
as a minor reaction of ester-containing compounds under
these conditions.
0a
2
is detrimental to the reaction, and only the starting
17
materials were isolated from the reaction. In contrast,
the Pauson-Khand cycloadduct was the only isolated
product from reactions in acetonitrile (MeCN) under a
2 2
N or H atmosphere (entries 6 and 7, respectively), even
Mech a n istic Stu d ies. To verify whether the observed
transformation is exclusive for Co (CO)12, cyclizations
4
in the presence of 5 equiv of 2-propanol (entry 8). These
findings also indicate that a large excess of 2-propanol
is necessary for these reactions. In 1,2-dichloroethane
using different sources of cobalt carbonyls under different
atmospheres were likewise investigated (Table 4). The
results in the table show that Pauson-Khand cycload-
(
(
DCE), a low yield of the bicyclopentenone was observed
entry 9).
dition occurred in all cases in 2-propanol whether Co
2
-
At the outset of this study, we assumed the interme-
(
CO) , Co (CO)12, or an enyne-Co (CO) complex was
8
4
2
6
diacy of a bicyclopentenone in the transformation of
enyne to bicyclopentanone where an in-situ 1,4-reduction
of the Pauson-Khand reaction cycloadduct occurred. This
is evident from the isolated bicyclopentenones and bicy-
lopentanones (Tables 2 and 4) and independent reduction
of the enone to the ketone (Table 2, entries 9-13). To
further verify this assumption, a series of reactions was
carried out in which the reactions were terminated at
different reaction times and the products were evaluated.
The results are summarized in Table 6 and indicate a
direct relationship between bicyclopentanone formation
and reaction time, although the yield was reduced after
prolonged reaction times (entries 1, 4-7). It is noteworthy
that in all cases, the enyne was completely consumed
within an hour of reaction as determined by TLC,
although no bicyclopentenone or dicobalthexacarbonyl
complexed alkyne was isolated after workup. This result
used, regardless of the reaction atmosphere. However,
since enone reduction occurred to varying degrees when
different metal carbonyl precursors were used, it is not
clear whether the reducing agent corresponds to the same
species in all cases. It further demonstrates that the
desired transformation is best achieved using Co
under a H atmosphere (cf. Table 2, entry 1 vs 4 and entry
vs 8). The results in Table 4 show that suppression of
4
(CO)12
2
7
bicyclopentanone formation was generally observed un-
der a CO atmosphere in reactions using all of the cobalt
carbonyl sources.
We next investigated the nature of the reaction sol-
vents and their effect on the efficacy of the reaction. Even
(
21) For cyclizations using catalytic amounts of Co
4
(CO)12, see ref
1
7 and references therein. See also (a) Belanger, D. B.; O’Mahony, D.
J . R.; Livinghouse, T. Tetrahedron Lett. 1998, 39, 7637. (b) Belanger,
D. B.; Livinghouse, T. Tetrahedron Lett. 1998, 39, 7641.

1
238 J . Org. Chem., Vol. 67, No. 4, 2002
Krafft et al.
Ta ble 6. Tim e Dep en d en ce of Bicyclop en ta n on e
F or m a tion : In ter m ed ia cy of Bicyclop en ten on e
Ta ble 7. Deu ter iu m La belin g Exp er im en ts: Rea ction s in
Deu ter a ted Solven ts
%
yield
%
yield
33:34c
entry
1
time (h)a
3
2
entry
1
solvent
3
1.5
1.5
1.5
8
14.5
15
-
17
5
-
-
-
-
13
28
43
43
48
56
37
b
i-PrOD
64
8
-
8
-
58
-
-
27 (1:0)
85 (1:7)
83 (1:0)
43 (1:4)
76 (1:6)
14 (1:3)
60 (1:5)
-
2
3
a
c
2
3
4
5
6
7
i-PrOD/HOAc
i-PrOD/DOAc
i-PrOH/HOAc
i-PrOH/DOAc
i-PrOD/i-PrOH
i-PrOD/i-PrOH/HOAc
2(d)-i-PrOH
a
4
5
6
7
b
a
a
24
b
a
d
In all cases the enyne was completely consumed within 1 h.
After 1.5 h, the reaction mixture was cooled to room temperature,
added with 5 equiv of NMO in CH2Cl2 and stirred at room
temperature overnight. After 1.5 h, the reaction mixture was
cooled to room temperature, added with 5 equiv of CAN in CHCl2
and stirred at room temperature overnight.
8
b
a
b
1
:1 volume ratio,
With 2 equiv of acetic acid, HOAc,
Determined from H NMR spectroscopy, 79% yield of 2. Dn )
deuterium substitution R to the carbonyl, n ) 1-4.
c
1
d
c
of the solvent with [Co(CO)
4
]- since reactions of cobalt
carbonyls with alcohols have been known to generate the
might suggest the formation of complexes or intermedi-
ates which were not isolable under standard workup
conditions.
latter (eq 3):25
3
Co (CO) + 24B h 4[CoB ][Co(CO) ] + 4CO (3)
4 12 6 4 2
The very low yield of the bicyclopentanone isolated
after 1.5 h prompted us to attempt intercepting any
organocobalt species presumably still unconverted to the
products (entry 1). Addition of oxidants common to the
Pauson-Khand reaction, such as N-methylmorpholine
N-oxide (NMO)22 and ceric ammonium nitrate (CAN),
at room temperature would presumably convert any
organocobalt intermediates to organic products, possibly
to the bicyclopentenone and/or bicyclopentanone. NMO
has been used to remove metal species as oxidized
clusters for easy workup after a typical thermal Pauson-
Khand reaction,7 and more extensively, to promote the
where B ) MeOH, EtOH, i-PrOH, t-BuOH.
Additionally, HCo(CO) has long been reported by
4
Orchin and others to promote 1,4-reductions of R,â-
10a
26
unsaturated ketones and aldehydes. Under their condi-
tions, HCo(CO)
dissociation of Co
4
was prepared independently from the
(CO) with N,N-dimethylformamide,
2
8
followed by acidification with HCl and an aqueous
workup. Although the reactions in this present work
proceeded under an atmosphere of either N or H , it was
2 2
found by Orchin that an atmosphere of CO was beneficial
to the reaction presumably by retarding the decomposi-
,23
2
2
Pauson-Khand reaction at ambient temperature. As
shown in entries 2 and 3, there was indeed a notable
increase in the yields of the bicyclopentanone with the
concomitant isolation of the bicyclopentenone. It was
speculated that the increase in products resulted from
conversion of intermediate organocobalt species to the
bicyclopentenone by addition of the oxidant.
2
6
tion of HCo(CO)
unsaturated ketones and aldehydes have likewise been
achieved using either Co (CO) at 140 °C under a total
pressure of 79 atm of CO and H
chiral phosphine ligand) at 110 °C under 30 atm of H
Our attempts, however, to independently generate HCo-
4
.
Catalytic hydrogenations of R,â-
2
8
2
7
2
2 6 2
or Co (CO) L * (L* )
28
2
.
2
9
Moreover, the possibility of enyne reduction to diene
prior to carbonylative cyclization was also addressed.
Diethyl diallylmalonate showed no reaction when sub-
(CO)
4
and simulate our reaction conditions were not
successful.
Thus, we proceeded to carry out a series of deuterium
labeling experiments using 2-propan(ol-d) assuming that
2
jected to these reaction conditions, under either a H or
CO atmosphere, excluding the possibility of carbonylative
cyclization of dienes. Over-reduction of bicyclopentanone
to bicyclopentanol also did not occur, as evident from the
recovery of the starting material when bicyclopentanone
reaction of Co
4
(CO)12 with 2-propan(ol-d) could provide
DCo(CO) or a similar cobalt carbonyl deuteride complex
4
(Table 7). We anticipated that deuterium would be
eventually incorporated at the ring-fusion carbon in place
2
was subjected to these reaction conditions. In addition,
no bicyclopentanol has been isolated from any of these
reactions.
(24) (a) Periasamy, M.; Lakshmi, M.; Rao, N. Rajesh, T. J . Organo-
met. Chem. 1998, 571, 183. Orchin, M. Acc. Chem. Res. 1981, 14, 259.
For an extensive review on HCo(CO) , see (b) Kemmitt, R. D. W.;
4
The results obtained thus far show that an efficient
enyne to saturated ketone conversion necessitates a
hydroxylic solvent. Further demonstrated from these is
the intermediacy of an enone that led us to speculate that
its transformation to the saturated ketone proceeded via
an in situ 1,4 reduction by a cobalt carbonyl hydride,
Russell, D. R. In Comprehensive Organometallic Chemistry; Abel, E.
W., Stone, F. A., Wilkinson, G., Eds.; Pergamon Press Ltd.: Oxford,
1
982; Vol. 5, p 1.
25) Manuel, T. A. Adv. Organomet. Chem. 1965, 3, 181. Wender,
I.; Sternberg, H. W.; Orchin, M. J . Am. Chem. Soc. 1952, 74, 1216.
26) (a) Goetz, R. W.; Orchin, M. J . Org. Chem. 1962, 27, 2698.
(
(
Goetz, R. W.; Orchin, M. J . Am. Chem. Soc. 1963, 85, 2782. (b) For
the conjugate reduction of R,â-unsaturated ketones using a Mn(III)
catalyst, see: Magnus, P.; Waring, M. J .; Scott, D. A. Tetrahedron Lett.
2
4
“HCo
x
(CO)
y
”. We presumed that a cobalt carbonyl
, could be generated from the reaction
2
000, 41, 9731 and references therein. These reactions were also
conducted in i-PrOH.
27) Ucciani, E.; Lai, R.; Tanguy, L. Compt. Rend. C. 1975, 281, 877.
hydride, HCo(CO)
4
(
(
22) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett.
990, 31, 5289.
23) Magnus, P.; Principe, L. M.; Slater. M. J . J . Org. Chem. 1987,
2, 1483.
(28) Maux, P. L.; Massonneau, V.; Simonneaux, G. J . Organomet.
Chem. 1985, 285, 101.
(29) Sternberg, H. W.; Wender, I.; Orchin, M. Inorg. Syntheses 1957,
Vol. V, 192.
1
(
5

Cobalt Carbonyl-Mediated Carbocyclizations
J . Org. Chem., Vol. 67, No. 4, 2002 1239
of hydrogen. Cyclization of enyne 1 in 2-propan(ol-d) gave
isotope effect in the reduction step, thus implying a
highly symmetrical transition state. On the basis of the
reaction conditions [Co (CO)12 in hot 2-propanol, 70 °C],
4
a hydrido cobalt carbonyl complex is the most plausible
reducing agent. Mechanistic possibilities for the reduction
include (a) an electron transfer that generates an enolate
radical anion followed by proton abstraction from the
solvent at the carbon â to the carbonyl; (b) a H atom
transfer to the enone via homolytic cleavage of the M-H
bond; or (c) a migratory insertion of a coordinated alkene
6
4% of the Pauson-Khand adduct 3 and 27% of deuter-
ated bicyclopentanone 33 (entry 1). This result is in
marked contrast to the cyclization in 2-propanol as the
solvent, in which the saturated ketone 2 was observed
as the sole product of the reaction, and was obtained in
higher yield (56%; Table 2, entry 4). As indicated in the
1
H NMR spectral data, deuterium had been incorporated
R to the carbonyl and also at the ring-fusion carbon of
the bicyclopentanone. Enolization at the R carbon has
been observed to occur under the typical Pauson-Khand
reaction conditions.30 On the other hand, a much im-
proved enyne to saturated ketone conversion (efficiency
and yield) was noted when acetic acid (HOAc) was used
as a cosolvent (i-PrOD: HOAc, 1:1 v/v) (entry 2 vs 1).
The use of a more acidic hydrogen source in the reaction
was thought to facilitate the formation of a cobalt
into a Co-H bond. Hydrogen atom transfer from HCo-
31,32
(CO)
4
to alkenes
has been observed to demonstrate
3
2-34
both inverse and normal deuterium isotope effects.
This reaction is thought to proceed by a H atom transfer
from the metal to the alkene to generate a cage radical
which, after cage escape, undergoes a subsequent H atom
abstraction. Inverse isotope effects are observed when H
atom transfer is reversible and generally result from a
situation where normal kinetic isotope effects are ob-
served for each individual reaction, but the isotope effect
for the reverse reaction is larger than the forward
reaction. Normal deuterium isotope effects are observed
carbonyl hydride, “HCo
DCo (CO) ”. The utility of an acid under the reductive
Pauson-Khand reaction conditions was first demon-
x y
(CO) ” or deuteride complex,
“
x
y
1
6
strated by Periasamy. It was observed that in the
presence of trifluoroacetic acid, cyclopentanones were
formed from the reactions of in situ generated cobalt
carbonyl alkyne complexes with norbornene under a CO
atmosphere.
when the H atom transfer is irreversible, with the reverse
reaction being slower than cage escape.3
2-35
In the
examples at hand, large normal deuterium isotope effects
have been observed suggesting that, if H atom transfer
from HCo(CO) to the alkene is the operative mechanistic
4
As anticipated a 1:1 mixture of i-PrOD and deuterated
acetic acid (DOAc) provided solely ketone 33 and in good
yields (entry 3 vs 2). Yet when only 2 equiv of HOAc was
used a lower yield of the saturated ketones was observed
along with a small amount of the enone 3 (entry 4 vs 2).
A 1:1 mixture of i-PrOH and DOAc, on the other hand,
gave exclusively the saturated ketones in good yields
pathway, the addition must be irreversible, most likely
due to the stability of the resulting radical. Conjugate
reduction of enones, such as 24 (Table 3), via an electron
transfer or hydrogen atom transfer should be facilitated
by stabilization of the incipient radical. However, under
the current conditions, the 2-phenyl-tetrasubstituted
enone 24 was not reduced to any appreciable extent and
only yielded small amounts of saturated ketone after
prolonged reaction times. The slow reduction of the
substituted enone and the large kinetic isotope effect
suggest that neither electron transfer nor hydrogen atom
transfer is the likely mechanistic processes.
(entry 5 vs 4). Interestingly, a 1:1 mixture of i-PrOD and
i-PrOH furnished 58% of enone 3 and the deuterated
ketones 33 and 34 (14%) (entry 6 vs 1 and Table 2, entry
4
). The yields of the saturated ketones from the reactions
carried out using the deuterated solvent is significantly
lower than the corresponding reaction carried out in
i-PrOH. We also observed that addition of 2 equiv of
HOAc into the reaction mixture using a 1:1 mixture of
i-PrOD and i-PrOH resulted in the sole formation of the
saturated ketones and in higher yield (entry 7 vs 6).
Meanwhile, when (2-d)-2-propanol was used as the
solvent, none of the Pauson-Khand cycloadduct 3 was
observed, the reaction only provided saturated ketone 2
Meanwhile, migratory insertions into metal-H bonds
have also been shown to exhibit normal deuterium
isotope effects.3
5-37
In the current cases, reduction of the
sterically hindered, tetrasubstituted alkenes did not
proceed (Table 3, entries 8-11), suggesting that a migra-
tory insertion via a symmetrical transition state, which
becomes more sluggish as the alkene substitution in-
creases, is the most plausible mechanistic route.
In conclusion, these deuterium labeling experiment
studies suggest that a metal hydride species is involved
in the product-determining step of the enone reduction,
as indicated by the strong H/D selectivity differences. Our
mechanistic studies further suggested that conversion of
(entry 8). This further demonstrates that the hydroxylic
hydrogen is the hydrogen that is being transferred to the
enone and not the methinyl hydrogen of 2-propanol. This
is likewise verified by the cyclization of enyne 1 using
i-PrOTMS as the solvent, which only gave 18% yield of
bicyclopentenone 3 as the sole product. The small amount
of the cycloadduct obtained from this reaction possibly
arose from the presence of small amounts of 2-propanol
derived from the probable hydrolysis of i-PrOTMS.
(
31) Feder, H. M.; Halpern, J . J . Am. Chem. Soc. 1975, 97, 7186.
(32) Eisenberg, D. C.; Norton, J . R. Isr. J . Chem. 1991, 31, 55.
33) Nalesnik, T. E.; Freudenberger, J . H. Orchin, M. J . Mol. Catal.
982, 16, 43.
34) Roth, J . A.; Wiseman, P.; Ruszala, L. J . Organomet. Chem.
1983, 240, 271.
35) Bullock, R. M. Isotope Effects in Reactions of Transition Metal
2
Conducting the reactions under a D atmosphere further
(
confirmed our hypothesis wherein no deuterium was
detected in the saturated ketones. This result suggests
that the hydrogen in the presumed cobalt carbonyl
hydride complex originated from the hydroxylic solvent
1
(
(
Hydrides. In Transition Metal Hydrides: Recent Advances in Theory
and Experiment; Dedieu, A., Ed.; VCH: New York, 1991.
and not from the H
2
atmosphere under which these
reactions were conducted.
The observed ratios of ketones 33 and 34 under the
present reaction conditions indicate a large kinetic
(36) Doherty, N. M.; Bercaw, J . E. J . Am. Chem. Soc. 1985, 107,
2
670.
37) Halpern, J .; Okamoto, T.; Zakhariev, A. J . Mol. Catal. 1976, 2,
(
65. Cooke, M. P.; Parlman, R. M. J . Am. Chem. Soc. 1975, 97, 6863.
Collman, J . P.; Finke, R. G.; Matlock, P. L.; Wahren, R.; Brauman, J .
I. J . Am. Chem. Soc. 1976, 98, 4685. Collman, J . P.; Finke, R. G.;
Matlock, P. L.; Wahren, R.; Komoto, R. G.; Brauman, J . I. J . Am. Chem.
Soc. 1978, 100, 1119.
(30) Krafft, M. E.; J uliano, C. A.; Wright, C.; Scott, I. L.; McEachin,
M. D. J . Am. Chem. Soc. 1991, 113, 1693. Krafft, M. E. J . Am. Chem.
Soc. 1988, 110, 968.

1
240 J . Org. Chem., Vol. 67, No. 4, 2002
Krafft et al.
Sch em e 2
the enyne to the saturated ketone proceeded via the
cyclopentenone, i.e., a sequential Pauson-Khand reac-
tion and 1,4-reduction. Mechanistic speculations on the
cobalt carbonyl-mediated tandem Pauson-Khand reac-
tion and 1,4-reduction of enynes is outlined in Scheme
alkyl cobalt intermediate has occurred presumably due
to the presence of HCo (CO) (Scheme 2). This observa-
x y
tion is reminiscent of our previous reports that dicobalt-
hexacarbonyl-complexed enynes could be transformed
into different carbocycles when heated in toluene under
different reaction conditions. Under a nitrogen atmo-
2
. A Co
Co (CO)
bonyl species liberated from the Pauson-Khand reaction
of an enyne-Co (CO) complex. Using Co (CO)12, active
cobalt carbonyl species were formed, possibly Co (CO)
2
(CO)
n
L
4
6-n species could be derived from either
(CO)12, or from the residual cobalt car-
6
2
8
or Co
sphere, 1,3 dienes were formed whereas in an oxygen-
7
ated atmosphere monocylic enones were obtained. In the
2
6
4
former case, an allylic C-H insertion was proposed to
occur in the metallacyclic intermediate. Interception by
molecular oxygen, presumably at the metal center, in this
intermediate was proposed in the latter. Most recently,
Gleason also reported the formation of vinyl cyclo-
pentenes from the thermolysis of highly substituted
2
8
3
8
or similar cobalt species, e.g., “Co
2 n
(CO) L6-n”, which
mediate the Pauson-Khand cyclization of the enyne to
the cyclopentenone.2
,39,40
Any unreacted or residual cobalt
carbonyl species could further undergo dissociation in the
presence of an excess of 2-propanol2 to presumably form
a cobalt carbonyl hydride, which has been known to
reduce R,â-unsaturated aldehydes and ketones to satu-
5
8
enynes under an argon atmosphere. Under these condi-
tions, the alkyl cobalt carbonyl intermediate was pro-
posed to undergo an allylic C-H activation followed by
a formal 5-endo-dig cyclization and generate vinyl cyclo-
pentenes. These accounts show that with a careful
manipulation of the reaction conditions the reactivity
of the dicobalthexacarbonyl-complexed enyne could be
diverted from the typical Pauson-Khand reaction path-
way to generate other carbocyclic and heterocyclic frame-
works.
2
7,28
rated aldehydes and ketones.
Moreover, the cobalt
carbonyl hydride is also invoked to induce reduction of
the alkyl cobalt complex and account for the observed
cycloalkenes (reductive cyclization, vide infra).
In comparison to previous protocols on the reductive
Pauson-Khand cyclization of enynes, the present pro-
cedure is more advantageous primarily due to its sim-
plicity and ease of operation. The evaluation is based on
the (a) in-situ generation of the enyne cobalt carbonyl
complex, (b) mildness of reaction conditions, (c) ease of
workup, and (d) availability of the cobalt carbonyl sources
Typically dicobalthexacarbonyl complexes of 1,6- and
1,7-enynes (or alkynes for intermolecular cyclizations
with alkenes) undergo Pauson-Khand reaction to give
bicyclic enones upon heating in aprotic solvents, such as
4
1
42
43
(
Co
strated the utility of Co
limited utility in organic synthesis compared to the
corresponding Co (CO)
complex.18
2
(CO)
8
, or Co
4
(CO)12). This work has further demon-
isooctane, 1,2-dichloroethane (DCE), acetonitrile,
benzene,
1
0c,44
20,44
4
(CO)12, which has been of more
1,2-dimethoxyethane (DME),
and tolu-
ene,45 under either a CO or an inert atmosphere (N
or
2
10c
46
2
8
Ar). Air or an oxygenated atmosphere has also been
B. Mon ocyclic Alk en e F or m a tion : Red u ctive Cy-
clization of En yn es. The novel transformation of enynes,
as cobalt carbonyl complexes, to monocyclic alkenes
described in Scheme 1 and exemplified briefly by the
results in Table 3 suggest a disruption of the standard
Pauson-Khand reaction pathway. A reduction of the
used in the Pauson-Khand cyclization of enynes. We
became interested in examining the effect of a H
2
atmosphere on the thermal reaction of enynes complexed
with cobalt carbonyls in toluene as the solvent, as the
precedents above suggest the possibility of new reactivity
patterns for this class of compounds. In fact, hydroformyl-
(
38) It was reported that under 1 atm of CO at 53 °C, a hexane
solution of Co (CO)12 would be converted to a solution in which 50% of
the cobalt content is present as Co (CO) (t1/ 2 ) 160 days). Bor, G.;
Dietler, U. K.; Pino, P. J . Organomet. Chem. 1978, 154, 301.
39) Co (CO)12 has been reported to react with alkynes to yield
alkyne-Co (CO)10 complexes. Under typical Pauson-Khand reaction
conditions, they might be expected to decompose to alkyne-Co (CO)
(41) Schore, N. E.; Croudace, M. C. J . Org. Chem. 1981, 46, 5436.
(42) (a) Sugihara, T.; Yamada, M.; Ban, H.; Yamaguchi, M.; Kaneko,
C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2801. (b) Sugihara, T.;
Yamada, M.; Yamaguchi, M.; Nishizawa, M. Synlett 1999, 771.
(43) Krafft, M. E.; Scott, I. L.; Romero, R. H.; Feibelmann, S.; Van
Pelt, C. E. J . Am. Chem. Soc. 1993, 115, 7199.
(44) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman,
M. I. J . Chem. Soc., Perkin Trans. 1 1973, 977.
(45) Billington, D. C.; Helps, I. M.; Pauson, P. L.; Thomson, W.;
Willison, D. J . Organomet. Chem. 1988, 354, 233. Gordon, A.; Johnstone,
C.; Kerr, W. J . Synlett 1995, 1083.
4
2
8
(
4
4
2
6
complexes, which are requisite initial complexes for the Pauson-Khand
reaction, and cobalt carbonyl complexes. Dickson, R. S.; Fraser, P. J .
Adv. Organomet. Chem. 1974, 12, 323. See also ref 17.
(40) Thommen, M.; Verentenov, A. L.; Guideti-Grept, R.; Keese, R.
Helv. Chim. Acta 1996, 79, 461.
(46) Stumpf, A.; J eong, N.; Sunghee, H. Synlett 1997, 205.

Cobalt Carbonyl-Mediated Carbocyclizations
J . Org. Chem., Vol. 67, No. 4, 2002 1241
Ta ble 8. Su r vey of Coba lt Ca r bon yl-Med ia ted Th er m a l
Cycliza tion s of En yn es u n d er a H2 Atm osp h er e
Ta ble 9. Tem p er a tu r e Effect on Red u ctive Cycliza tion s
of En yn e-Co2(CO)6 Com p lexes
%
yield
37 (endo/exo)a
cobalt carbonyl
CyNH2
(no. of equiv)
36
(% yield)
temp
(°C)
time
(h)
a
entry
complex
solvent
3
1
2
3
4
5
6
7
8
9
“Co2(CO)6” c
Co2(CO)8
Co2(CO)8
Co2(CO)8
Co4(CO)12
Co4(CO)12
Co4(CO)12
Co4(CO)12
Co4(CO)12
0
0
3
3
0
1.5
3
0
6
toluene
toluene
toluene
DME
toluene
toluene
DME
-b
29
70
74
60
70
80
90
5
5
5
2
16
14
16
21
52 (1:1)
34 (2:1)
59 (3:1)
6 (4:1)
b
-
77
a
Ratio of endo and exo alkenes.
78, 85d
16
DME
DME
Co
) albeit it was obtained in low yield in DME in the
absence of CyNH (entry 8). Thermolysis of enyne 35 in
toluene using Co (CO)12 gave a mixture of alkenes instead
4
(CO)12 was used in the cyclizations in toluene (entry
82
5
a
b
Entries 5-7: 50 mol % Co4(CO)12,
Mixture of alkene
2
c
isomers, no bicyclopentenone 36. Isolated enyne-Co2(CO)6 com-
plex. 70 °C.
4
d
17
of the bicyclopentenone (entry 5). Once again, addition
of cyclohexylamine resulted in good yields of cyclopen-
tenones from reactions carried out in toluene (entry 6)
and DME (entry 9). It is apparent from these results that
the desired transformation could be best achieved ther-
mally in a noncoordinating solvent, e.g., toluene, or in
the absence of coordinating ligands, such as DME or
cyclohexylamine. These results are encouraging because
suppression of the normal Pauson-Khand reaction route
is evident, albeit optimization studies needed to be
pursued further.
On the contrary, under the amine-N-oxide-promoted
2
reaction conditions a H atmosphere did not influence the
fate of these reactions and cyclopentenones were obtained
in good yields (eq 5). Amine-N-oxide promoted protocols
are typically carried out under either a nitrogen, argon,
or oxygen atmosphere (for Me NO only).
3
ations of alkenes using cobalt carbonyl complexes are
generally performed under a mixture of H
synthesis gas), although at elevated pressures.47
P r elim in a r y Stu d ies. In a preliminary study, a
toluene solution of the dicobalthexacarbonyl complex of
enyne 35 was heated at 80 °C under a H atmosphere
eq 4). The crude mixture of products seemingly showed
no Pauson-Khand cycloadduct, but rather a mixture of
monocyclic alkenes. The normal route to the Pauson-
Khand cycloadduct had apparently been interrupted
2
and CO gases
(
2
(
under the H
CO) complex in the presence of H
2
atmosphere. Thermolysis of an enyne-Co
2
-
(
6
2
proceeded to give
rise to a reductive cyclization to furnish monocyclic
alkenes.48 We explored these interesting and novel
observations, and herein we describe the development of
another interruption of the normal Pauson-Khand reac-
tion pathway.6
10a,22
-9
We initially set out to determine whether a disruption
of the normal Pauson-Khand reaction pathway was
2
general under a one atmosphere of H . Our preliminary
results are summarized in Table 8. Interestingly, ther-
molysis of the dicobalthexacarbonyl complex of enyne 35
Op tim iza tion of Rea ction Con d ition s. It had been
demonstrated in our preliminary studies that a reductive
cyclization of an enyne-Co (CO) complex to generate
2 6
monocyclic alkenes was favored in a noncoordinating
solvent, e.g., toluene, although it appeared not to be
optimal yet (Table 8). We then proceeded to determine
the most appropriate temperature for these cyclizations
in toluene under a H atmosphere yielded no Pauson-
2
Khand cycloadduct but gave a complex mixture of alkene
products (entry 1). Similar observations were noted using
(
Table 9). In addition to incomplete suppression of
Co
tained in low yield (entry 2). The presence of cyclohexyl-
amine (CyNH ) in the reaction significantly improved the
2 8
(CO) , although the bicyclopentenone was also ob-
cyclopentenone formation, the table shows variable yields
of monocyclic alkenes from cyclizations carried out at
different temperatures. The effect of different solvents
on the fate of these cyclizations at 60 °C was also
examined, and the results confirmed that the desired
transformation could indeed be best achieved in toluene
despite the formation of cyclopentenones (Table 10). The
desired monoalkene products have not been observed
from reactions conducted in DMSO and acetonitrile.
These results evidently indicated that a mere change in
2
yield of the cyclopentenone and suppressed the formation
of the alkene products in toluene (entry 3) and DME
entry 4). It has been shown that cyclohexylamine is
(
beneficial in enhancing the efficiency of thermal Pauson-
2
0
Khand reactions. No cyclopentenone was observed when
(
47) For recent review on hydroformylations, see Ojima, I.; Tsai, C.-
H.; Tzamarioudaki, M.; Bonafoux, D. Org. React. 2000, 56, 1.
48) Enynes have also been known to undergo cycloisomerizations
(
2 2
the atmosphere from N to H at one atmosphere is
insufficient to effect a complete disruption of the normal
in the presence of other transition metal complexes. For a recent
leading reference, see Cao, P.; Zhang, X. Angew. Chem., Int. Ed. 2000,
3
9, 4104.
route in the Pauson-Khand reaction pathway. These

1
242 J . Org. Chem., Vol. 67, No. 4, 2002
Krafft et al.
Ta ble 12. Su r vey of Ad d itives for Red u ctive
Ta ble 10. Su r vey of Solven ts for Red u ctive Cycliza tion s
of En yn e-Co2(CO)6 Com p lexes
Cycliza tion s of En yn e-Co2(CO)6 Com p lexes
%
yield
% yield
temp
time
(h)
37 (endo/exo)a
entry
additives
(°C)
3
37 (endo/exo)a
solvent
3
26b
1
2
3
4
5
6
7
8
9
0
1
2
3
Et SiH
(EtO)3SiH
Cl3SiH
60
60
70
60
60
60
70
70
70
70
70
70
70
-
-
62 (3:1)
40
20
60
66
52
33 (2.5:1)
30 (1:1)
27 (1:1)
33
26
27
dimethyl sulfoxide
acetonitrile
2
2
2.5
4
5
-
3
75
36
25
16
10
-
1
,2-dimethoxyethane
10 (2:1)
36 (1:1)
52 (1:1)
22 (2:1)
23
-
dichloroethane
toluene
hexane
Ph2MeSiH
PhMe2SiH
Ph2SiH2
-
-
2
PMHSb
15
23
18
10
22
21
15
a
Ratio of endo and exo alkenes. b 41% enyne 1.
Bu3SnHc
Ta ble 11. Et3SiH-In d u ced Red u ctive Cycliza tion s of
1
1
1
1
Ph3SnH
catecholborane
9-BBN
En yn e-Co2(CO)6 Com p lexes
BH3‚THF
29
a
The yields correspond to the isolated endo alkene only unless
b
otherwise the ratio of the endo to exo alkenes is indicated. PMHS
polymethyl hydrosiloxane, 10 mol % Bu3SnH.
c
)
%
yield
Et3SiH
(mol %)
temp
(°C)
time
(h)
37 (endo/exo)a
It was further observed that the amount of the reduc-
entry
3
ing agent is critical in the reaction. While a lower amount
of the additive resulted in the formation of bicyclopen-
tenone at 60 °C (entries 1 and 2), higher amounts led to
a reversal of the product ratio, in addition to a decrease
in yield (entry 5). The use of a stoichiometric amount of
1
2
3
4
5
6
7
10
10
25
25
50
10
25
60
60
60
60
60
80
80
1
2
2
15
2
15
15
14
27
-
30 (1:1)
40 (1:1)
62 (3:1)
29 (3:1)
6 (2:1)
-
21
-
-
27 (4:1)
41 (8:1)
3
Et SiH effected incorporation of alkyl silane into the
starting material. It was also observed that a prolonged
reaction time led to reduction in yield although none of
the cyclopentenone was isolated (entry 4). Furthermore,
reactions conducted at 80 °C gave lower yields of the
monocyclic alkenes (entries 6 and 7). It is also noteworthy
that incremental addition of NMO (1 equiv × 5) to the
a
Ratio of endo to exo alkenes.
results further suggested that under these conditions
insertion of CO into a cobalt-carbon bond in the metal-
lacycle is presumably competitive with reduction.
Meanwhile, the utility of triethylsilane under the
thermally promoted Pauson-Khand reaction conditions
has been demonstrated.2 It was used as an additive
in PK reactions to generate, via a reductive decomplex-
ation,49 an active cobalt carbonyl species from an alkyne-
3
reaction in eq 5, in the presence of 1.3 equiv of Et SiH,
resulted in only 45% of enone 3. Unfortunately, our
attempts to carry out deuterium labeling experiments
1b
and understand the role of Et
failed.
3
SiH in these reactions
Co
of enynes under one atmosphere of CO. Encouraged by
these findings, we pursued our studies using Et SiH as
2
(CO)
6
complex, which catalyzed efficient cyclizations
To further improve the efficiency in these cyclizations
other hydride sources were also screened (Table 12).
3
Among the alkylsilanes surveyed, Et
3 2
SiH, Ph MeSiH,
an additive with the hope that metallacycle reduction
would occur at a faster rate than CO insertion, providing
an interruption of the Pauson-Khand reaction path-
way.50
The effect of triethylsilane on the thermolysis of an
2 6 2
enyne-Co (CO) complex under a H atmosphere was
then investigated. As shown in Table 11, a complete
PhMe SiH, and Ph SiH behaved equally well (entries
2
2
2
1, 4-6). It is noteworthy that addition of a less reactive
silane, poly(methylhydrosiloxane) (PMHS) did not pro-
vide a significant difference in the reaction (entry 7
compared to Table 9, entry 2, without PHMS). Cycliza-
tion reactions with tin and boron hydrides as additives
gave lower yields as did the corresponding reactions
with hydrosilanes. A mixture of cyclopentenone and
monocyclic alkene was observed in all of these cases
suppression of the Pauson-Khand reaction was indeed
achieved in the thermolysis of enyne-Co
2
(CO)
6
complex
(
entries 3 and 7-13). In addition to Et
pinacolborane, (EtO) SiH, and Bu SnH had been used by
Livinghouse in their studies on the generation of the
active cobalt carbonyl species from an alkyne-Co (CO)
SiH, which behaved as well
SiH, these additives proved less effective for
3
SiH, PMHS,
1
a using 25 mol % of Et
3
SiH at 60 °C (entry 3). A mixture
of the endo- and exo-alkene isomers of 37 was obtained
as the only products.
3
3
2
6
complex.2 Except for (EtO)
as Et
1b
3
(
49) Hokosawa, S.; Isobe, M. Tetrahedron Lett. 1998, 39, 2609.
(50) During these studies, it was reported by Widenhoefer that high-
3
yielding and highly selective cycloisomerizations of functionalized 1,6-
catalyst generation in the studies by Livinghouse.
Scop e a n d Lim ita tion s. The scope of these observa-
tions was then examined in the thermolyses of several
dienes to form 1,2-disubstituted cyclopentenes using catalytic amounts
3
of cationic (π-allyl)palladium complex, [η -(C
3
H
5
)Pd(OEt)
2
PCy
3
]BAr
4
]
Ar)3,5-C
6
H
3
(CF
3
)
2
, could be achieved in the presence of Et
Triethylsilane was presumed to facilitate the formation of the active
3
SiH.
1
2 6
,6- and 1,7-enyne-Co (CO) complexes (Table 13). We
palladium hydride species. Pei, T. Widenhoefer, R. A. Tetrahedron Lett.
observed modest yields in these reactions and were
disappointed to discover that this observation is quite
2
1
000, 41, 7597. Widenhoefer, R. A.; Perch, N. S. Org. Lett. 1999, 1,
103.

Cobalt Carbonyl-Mediated Carbocyclizations
J . Org. Chem., Vol. 67, No. 4, 2002 1243
Ta ble 13. Red u ctive Cycliza tion s of En yn e-Co2(CO)6 Com p lexes
a
Reactions were carried out at a substrate concentration of 0.05 M in toluene at 60 °C under a H2 atmosphere, without or with 25 mol
%
of Et3SiH. Enyne-Co2(CO6) complexes were prepared from the corresponding enyne and Co2(CO)8 and were isolated prior to the reactions.
b
Reactions were typically completed in 1-2 h. Yield of endo alkene isomer except for entry 1 where a mixture of isomers was obtained.
c
Ratio of endo to exo alkene isomers. Ph2SiH2. Ph2MeSiH. f PhMe2SiH.
d
e
variable. Nevertheless, these studies demonstrated the
formation of monocyclic alkenes from the reductive
cyclization of enynes, via their cobalt carbonyl complexes.
Pauson-Khand reaction mechanistic pathway, were also
observed under these reaction conditions.
Furthermore, thermolyses of dicobalthexacarbonyl-
complexed enynes under a hydrogen atmosphere led to
reductive cyclizations to form monocyclic alkenes in
moderate yields, in addition to the expected bicyclopen-
tenone product. In most cases, addition of a hydrosilane
in the reaction induced a complete suppression of the
bicyclopentenone formation. These results demonstrate
another example of an interruption of the normal route
in the Pauson-Khand reaction pathway and are the first
examples of such transformations using this class of
complexes.
3
We speculated that the presence of Et SiH has induced
a reduction of the alkyl cobalt complex demonstrating an
interruption in the Pauson-Khand reaction pathway
with the consequent formation of another carbocylic
framework.
Su m m a r y a n d Con clu sion s
Thermolyses of dicobalthexacarbonyl-complexed enynes,
under different reaction conditions, have resulted in the
generation of different carbocyclic frameworks. Bicyclo-
pentanones were formed from enyne-Co
or enynes that were treated with Co (CO)12 or Co
in an alcoholic solvent under a H or N atmosphere.
Although the present protocol necessitated a stoichio-
metric quantity of Co (CO)12, this provided an extension
of the utility of this tetranuclear cobalt cluster in organic
transformations. We speculated that an in situ 1,4-
reduction of the intermediate bicyclopentenone (from the
2
(CO)
6
complexes,
Exp er im en ta l Section
4
2
(CO)
8
Compounds 1, 3, 4, 9, 10, 12, 15, 23, 25, 30, 35, 36, 38, and
2
2
2
0
4
0 have been previously synthesized and characterized. All
1
protons were assigned with the aid of H NOE or decoupling
experiments. Commercially available Co (CO) and Co (CO)12,
4
2
8
4
purchased from Strem Chemicals, MA, were stored in the
freezer and used without further purification.
A. Bicyclo[3.3.0]octa n on e F or m a tion : Red u ctive P a u -
son -Kh a n d Rea ction of En yn es. 1. Rep r esen ta tive Ex-
2 6
p er im en ta l P r oced u r es. P r ep a r a tion of En yn e-Co (CO)
4
Pauson-Khand reaction) by the metal hydride HCo(CO) ,
that is presumably generated from the reaction of
residual cobalt carbonyl complexes with an excess of
Com p lexes. To a solution of enyne 1 (101 mg, 0.42 mmol) in
petroleum ether (4.0 mL) was added Co (CO) (160 mg, 0.47
mmol), and the mixture was stirred at room temperature for
h (or until complex formation was complete by TLC).
2
8
2
-propanol, is responsible for bicyclopentanone formation.
It was also determined that the hydroxylic hydrogen is
the hydrogen that is being transferred into the enone.
In several cases monocyclic alkenes, which arise from the
reduction of the alkyl cobalt carbonyl intermediate in the
1
Filtration through a short pad of Celite (eluent petroleum
ether) followed by concentration under reduced pressure at
room temperature gave a quantitative yield of enyne-Co (CO)
2 6

1
244 J . Org. Chem., Vol. 67, No. 4, 2002
Krafft et al.
1
132.28, 119.08, 61.14, 57.15, 36.65, 14.03. IR (cm-1): 2983,
2363, 1732, 1642, 1445, 1368, 1286, 1217, 1144, 1036, 921. MS
[EI, m/z (rel intensity)]: 93.1, 153.1 (100), 240.3 (M ). Anal.
complex 1a . H NMR (CDCl
3
2
, 300 MHz): δ 5.98 (s, 1H, CH -
CCH), 5.68 (dddd, J ) 17.5, 10.1, 7.4, 7.4 Hz, 1H, CHdCH
2
),
.18 (dm, J ) 10.1 Hz, 1H, CHdCHH), 5.13 (dm, J ) 17.0 Hz,
H, CHdCHH), 4.27 (dq, J ) 14.8, 7.4 Hz, 2H, 2 CH O), 4.17
O), 3.62 (2, 2H, CH CCH),
CHdC), 1.26 (t, J ) 7.4 Hz, 6H,
+
5
1
(
2
Calcd for C13
8.35.
20 4
H O : C, 64.98; H, 8.39. Found: C, 65.11; H,
dq, J ) 14.1, 7.4 Hz, 2H, 2 CH
2
2
2. En yn es. En yn e 6:51 1H NMR (CDCl , 300 MHz): δ 5.60
2
2
.76 (d, J ) 7.4 Hz, 2H, 2 CH
2
3
CH ).
3
(dqt, J ) 15.9, 7.4, 1.7 Hz, 1H, CH CHdCHCH ), 5.22 (dddq,
2
3
Typ ica l Red u ctive P a u son -Kh a n d Cycliza tion P r o-
tocol (for the reactions depicted in Table 3). In a round-bottom
vessel equipped with a three-way stopper and a balloon of H
a mixture of enyne 1 (27 mg, 0.11 mmol) and Co (CO)12 (65
mg, 0.11 mmol) was pumped briefly and purged three times
with H . i-PrOH (23.0 mL) was then added, and the mixture
was heated at 70 °C for 16 h. Upon completion of the reaction,
the purple to pink mixture was cooled to room temperature,
concentrated in vacuo, diluted with EtOAc, and plugged
through a pad of silica gel. Subsequent removal of the solvent
and purification by flash chromatography (SiO , 20% EtOAc
2
in hexanes) afforded 20 mg of bicyclopentanone 2 (67% yield)
as a colorless oil.
A similar general procedure was used for the reactions
depicted in the following:
a) Table 2, except for the reactions conducted under a N
or a CO atmosphere, which replaced the H atmosphere, and
the use of enyne 4, which was mixed with enone 3 prior to
evacuation and purging of the system.
b) Table 4, where Co
were used as alternatives for Co
atmosphere was replaced with either a N
c) Table 5, where 2-propanol was replaced with the ap-
propriate solvent. In entry 8, 5 equiv of 2-propanol was added
as a solution in acetonitrile.
d) Table 6, entries 1, 4-7, where the reactions were stopped
at different reaction times. For entries 2 and 3, the reaction
mixtures were heated at 70 °C for 1.5 h, cooled to room
J ) 15.9, 7.4, 7.4, 1.7 Hz, 1H, CH CHdCHCH ), 4.20 (q, J )
2
3
7.0 Hz, 4H, (CH CH O C) × 2), 2.77 (d, J ) 2.9 Hz, 2H, CH -
3
2
2
2
2
,
CCH), 2.72 (d, J ) 7.4 Hz, 2H, CH CHdCHCH ), 2.00 (t, J )
2
3
4
2.5 Hz, 1H, CH CCH), 1.64 (dm, J ) 6.6 Hz, 3H, CH CHd
2
2
CHCH ), 1.24 (t, J ) 7.0 Hz, 6H, (CH CH O C) × 2).
3
3
2
2
52 1
2
En yn e 7: H NMR (CDCl , 300 MHz): δ 7.20-7.36 (m,
3
5
6
H, aromatic H), 6.52 (d, J ) 16.1 Hz, 1H, CH
.02 (dt, J ) 15.4, 7.4 Hz, 1H, CH CHdC ), 4.23 (q, J ) 7.4
CH CHd
C) × 2), 2.96 (d, J ) 6.7 Hz, 2H, CH
), 2.84 (d, J ) 2.7 Hz, 2H, CH CCH), 2.06 (t, J ) 2.7
Hz, 1H, CH CCH), 1.26 (t, J ) 7.4 Hz, 6H, (CH CH
C) ×
).
En yn e 8. To a solution of N-allyl-4-methylbenzenesulfona-
2 6 5
CHdCHC H ),
2
6 5
H
Hz, 4H, (CH
CHC
3
2
O
2
2
6
H
5
2
2
3
2 2
O
2
mide (148 mg, 0.694 mmol) in THF/DMSO (5/2 mL) was slowly
added sodium hydride (31 mg, 0.763 mmol, 60% dispersion in
mineral oil). After stirring for 15 min at room temperature,
propargyl bromide (0.08 mL, 0.763 mmol, 80% solution in
toluene) was added dropwise. Next, the reaction mixture was
heated at 70 °C and continued to stir under N for 30 min.
2
After quenching with water and removal of most of the solvent,
the solution was diluted with ethyl acetate, washed twice with
(
2
2
(
2
(CO)
8
and enyne-Co
(CO)12 and the H
or a CO atmosphere.
2 6
(CO) complex
1
a
4
2
2
brine, dried over MgSO
tion by flash column chromatography (SiO
hexanes) provided 157 mg (90%) of enyne 8 as a colorless oil
, and concentrated in vacuo. Purifica-
4
(
2
, 12% EtOAc in
1
3
that later solidified upon cooling. H NMR (CDCl , 300 MHz):
(
δ 7.72 (d, J ) 8.7 Hz, 2H, aromatic Hortho), 7.28 (d, J ) 8.7 Hz,
meta
2
H, aromatic H
CHCH
.07 (d, J ) 2.7 Hz, 2H, CH
CH CHdCHCH ), 2.41 (s, 3H, CH
Hz, 1H, CH CCH), 1.68 (d, J ) 6.0 Hz, 3H, CH
Anal. Calcd for C14 S: C, 63.85; H, 6.51; N, 5.32.
Found: C, 63.73; H, 6.41; N, 5.37.
), 5.70 (dq, J ) 15.4, 6.7, 1H, CH
2
CHd
CHdCHCH ),
CCH), 3.74 (d, J ) 6.7 Hz, 2H,
SO N), 1.97 (t, J ) 2.7
CHdCHCH ).
3
), 5.35 (dtd, J ) 14.8, 6.7, 2.0 Hz, 1H, CH
2
3
temperature, added with either NMO in CH
equiv) or CAN in CH Cl
(entry 2, 5 × 1 equiv), and stirred
at room temperature overnight.
e) Table 7, where 2-propanol was replaced with the ap-
propriate premixed deuterated solvent systems and the H
atmosphere by N
2
Cl
2
(entry 2, 5 ×
4
2
1
2
2
2
3
3
C
6
H
4
2
2
2
3
(
H
17NO
2
2
2
.
53 1
En yn e 11: H NMR (CDCl
H, aromatic H), 7.27-7.31 (m, 3H, aromatic H), 5.69 (ddt, J
17.5, 10.1, 7.4 Hz, 1H, CH CHdCH ), 5.21 (dm, J ) 16.8
Hz, 1H, CH CHdCHH), 5.14 (dm, J ) 10.1 Hz, 1H, CH CHd
CHH), 4.22 (q, J ) 7.4 Hz, 4H, (CH CH
C) × 2), 3.01 (s,
H, CH CCC ), 2.86 (d, J ) 7.4 Hz, 2H, CH CHdCH ), 1.26
t, J ) 7.4 Hz, 6H, (CH CH
C) × 2).
En yn e 13: H NMR (CDCl , 300 MHz): δ 7.42-7.48 (m,
H, aromatic H), 7.28-7.34 (m, 3H, aromatic H), 5.95 (ddt, J
17.5, 10.7, 5.4 Hz, 1H, CH CHdCH ), 5.35 (ddt, J ) 17.5,
.0, 1.3 Hz, 1H, CH CHdCHH), 5.24 (dd, J ) 10.1, 1.3 Hz,
H, CH CHdCHH), 4.38 (s, 2H, CH CCC ), 4.14 (dm, J )
.4 Hz, 2H, CH CHdCH ).
En yn e 14:5 H NMR (CDCl
5.4, 6.0 Hz, 1H, CH CHdCHCH
.4 Hz, 1H, CH CHdCHCH ), 4.19 (q, J ) 6.7 Hz, 4H,
CH CCCH , CH CHd
C) × 2), 2.66-2.75 (m, 4H, CH
CHCH ), 1.75 (t, J ) 2.7 Hz, 3H, CH CCCH ), 1.64 (d, J ) 5.4
Hz, 3H, CH CHdCHCH ), 1.23 (t, J ) 6.7 Hz, 6H, (CH
CH
C) × 2).
3
, 300 MHz): δ 7.33-7.41 (m,
Syn th esis of Bicyclop en ta n on e 2 via Hyd r ogen a tion .
To a 10 mL round-bottom flask equipped with a three-way
stopper saturated with argon atmosphere were added ca. 10
mg of Pd/C and ethanol (2.5 mL). It was then pumped briefly
and purged three times with a hydrogen gas. A solution of
enone 3 (28 mg, 0.11 mmol) in ethanol (1.5 mL) was added,
and the mixture was stirred at room temperature for 15.5 h.
After concentration, the residue was washed with EtOAc (4 ×
2
)
2
2
2
2
3
2 2
O
2
(
2
6
H
5
2
2
3
2 2
O
53
1
3
2
)
2
1
5
1
0 mL), where the combined organic layers were washed with
2
2
brine, dried (Na
coarse silica gel. Concentration in vacuo and purification by
flash chromatography (SiO , 50% EtOAc in hexanes) yielded
5 mg (89%) of bicyclopentanone 2.
P r ep a r a tion of Dieth yl Dia llylm a lon a te. To a cooled
suspension (0 °C) of hexane-washed NaH (454 mg, 11.4 mmol,
0% dispersion in mineral oil) in THF (18.0 mL) was added
dropwise a solution of diethyl allylmalonate (1.1 g, 5.6 mmol)
in THF (7.0 mL). Ten minutes after addition was completed
the bath was removed, and the reaction mixture was allowed
to warm to room temperature. After being stirred for 30 min,
it was cooled to 0 °C, and allyl bromide (2.0 mL, 23 mmol)
was added dropwise. It was then stirred overnight with the
bath warming to room temperature. After being quenched with
2 4
SO ), and filtered through a short plug of
2
2
2
6 5
H
2
2
2
2
4 1
3
, 300 MHz): δ 5.57 (dqm, J )
), 5.22 (dtm, J ) 14.8, 7.4,
1
7
2
3
2
3
6
(CH
3
2
O
2
2
3
2
3
2
3
2
3
3
-
2
O
2
E n yn e 16. To a cooled solution (0 °C) of diethyl allyl-
malonate (4.045 g, 20.2 mmol) in THF (100 mL) was slowly
added sodium hydride (877 mg, 36.6 mmol, 60% dispersion in
mineral oil). Five minutes after the sodium hydride had been
added, the ice bath was removed. After stirring for 30 min at
room temperature, the mesylate of 3-butyn-1-ol (3.285 g, 22.2
mmol) was added dropwise. The reaction mixture was then
2
1
N HCl at 0 °C, the mixture was extracted with EtOAc (3 ×
5 mL), and the combined organic layers were successively
washed with 2 N HCl, saturated NaHCO
over Na SO , and concentrated in vacuo. Purification by flash
chromatography (SiO , 6% EtOAc in hexanes) provided 902
mg (67%) of diethyl diallylmalonate as a colorless oil. H NMR
CDCl , 300 MHz): δ 5.65 (dddd, J ) 16.8, 9.6, 7.4, 7.4 Hz,
H, 2 CHCdCH ), 5.13 (d, J ) 16.1 Hz, 2H, 2 CHdCHH), 5.10
d, J ) 10.1 Hz, 2H, 2 CHdCHH), 4.19 (q, J ) 7.4 Hz, 4H, 2
OCH ), 2.64 (d, J ) 7.4 Hz, 4H, 2 CH CHdC), 1.25 (t, J ) 7.4
Hz, 6H, 2 CH ). C NMR (CDCl , 75 MHz): δ 170.71,
3
, and brine, dried
2
4
2
1
(51) Grigg, R.; Stevenson, P.; Worakun, T. Tetrahedron 1988, 44,
4
967.
52) Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J . Am. Chem.
Soc. 1994, 116, 6049.
53) Grossman, R. B.; Buchwald, S. L. J . Org. Chem. 1992, 57, 5803.
(
3
(
2
2
(
(
2
2
(54) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J . Am. Chem.
Soc. 1999, 121, 5881.
1
3
2
CH
3
3

Cobalt Carbonyl-Mediated Carbocyclizations
heated at reflux under N for 24 h. After being quenched with
J . Org. Chem., Vol. 67, No. 4, 2002 1245
O). Anal. Calcd for C15 S: C, 61.41; H, 6.53; N, 4.77.
2
H19NO
3
water, most of the solvent was removed under vacuo. The
reaction mixture was then diluted with diethyl ether, washed
Found: C, 61.35; H, 6.56; N, 4.76.
Bicyclop en ta n on e 21: 1H NMR (CDCl , 500 MHz): δ 5.02
3
twice with brine, dried over MgSO
Purification by flash column chromatography (SiO
4
, and concentrated in vacuo.
(qq, J ) 6.1, 6.1 Hz, 1H, OCH(CH ) ), 3.74 (s, 3H, OCH ), 2.70
3
2
3
2
, 5% EtOAc
(dd, J ) 14.1, 7.1 Hz, 1H, CH CHCHHCdO), 2.45 (m, 2H,
2
in hexanes) followed by distillation under vacuo (to remove
remainder of diethyl allylmalonate) and a second chromatog-
CH CHCH CdO and CHHCHCH CdO), 2.44 (AB, J ) 14.4
2
2
2
AB
Hz, 1H, CH CCH CHHCdO), 2.36 (AB, J
AB
2
3
) 14.4 Hz, 1H,
1
raphy afforded 1.734 g (34%) of enyne 16 as a colorless oil. H
CH CCH CHHCdO), 2.34 (br AB, J AB ) 18.5 Hz, 1H,
2
3
NMR (C
6
D
6
, 500 MHz): δ 5.66 (ddt, J ) 17.1, 10.3, 7.3 Hz,
CHdCH ), 4.96 (obscured ddt, J ) 17.1, 2.0, 1.5 Hz,
CHdCHH), 4.93 (obscured dm, J ) 9.8 Hz, 1H,
CHHCCH CH CdO), 2.24 (br dm, J ) 18.5 Hz, 1H, CHHCH-
3
2
1
1
H, CH
H, CH
2
2
CH CdO), 2.15 (br AB, J ) 18.8 Hz, 1H, CHHCCH CH Cd
2
AB
3
2
2
O), 2.02 (dd, J ) 13.8, 8.7 Hz, 1H, CH CHCHHCdO), 1.21 (d,
2
CH
CH
CH
2
3
3
CHdCHH), 3.90 (ABq, J AB ) 16.6, J ) 7.0 Hz, 2H,
J ) 6.7 Hz, 6H, OCH(CH ) ), 1.19 (s, 3H, CH CCH CH CdO
3
2
2
3
+
2
CH
2
O
2
C), 3.88 (ABq, J AB ) 16.6, J ) 7.0 Hz, 2H,
C), 2.75 (d, J ) 7.3 Hz, 2H, CH CHdCH ), 2.34-
CH CCH), 2.22 (td, J ) 8.8, 2.4 Hz, 2H,
CCH), 1.73 (t, J ) 2.4 Hz, 1H, CH CH CCH), 0.86 (t,
J ) 7.3 Hz, 6H, (CH CH
C) × 2). Anal. Calcd for C14
C, 66.65; H, 7.99. Found: C, 66.61; H, 8.08.
MS [EI, m/z (rel intensity)]: 109.0 (100), 282.2 (M ).
CH
2
O
2
2
2
Bicyclop en ta n on e 22:
1
H NMR (CDCl , 300 MHz): δ 3.75
3
2
.40 (m, 2H, CH
2
2
(s, 3H, OCH ), 3.72 (s, 3H, OCH ), 2.72 (dd, J ) 14.1, 7.4 Hz,
3
3
CH CH
2
2
2
2
1H, CH CHCHHCdO), 2.39-2.52 (m, 4H), 2.33 (br AB, J
)
2
AB
3
2
O
2
H
20
O
4
:
,
18.1 Hz, 1H, CH CCH CHHCdO), 2.20 (br dm, J ) 14.8 Hz,
2
3
1H, CHHCHCH CdO), 2.15 (br AB, J ) 18.1 Hz, 1H, CH -
2
AB
2
1
3
. Cycloa d d u cts. Bicyclop en ta n on e 2: H NMR (CDCl
3
CCH
CHCHHCdO), 1.18 (s, 3H, CH
En on e 24:55 1H NMR (CDCl
5H, aromatic H), 4.28 (q, J ) 6.7 Hz, 2H, CH
4.22 (m, 2H, CH CH C), 3.65 (AB, J AB ) 18.8 Hz, 1H,
CHHCdCC CdO), 3.29 (AB, J AB ) 18.8 Hz, 1H, CHHCd
CC CdO), 3.14 (m, 1H, CH CHCH CdO), 2.83 (obscured dd,
J ) 12.8, 7.7 Hz, 1H, CHHCHCH CdO), 2.82 (obscured dd, J
) 17.7, 6.6 Hz, 1H, CH CHCHHCdO), 2.32 (dd, J ) 17.8, 2.7
Hz, 1H, CH CHCHHCdO), 1.77 (dd, J ) 12.8, 12.8 Hz, 1H,
3
CHHCdO), 2.03 (dd, J ) 14.1, 9.4 Hz, 1H, CH
CCH CH CdO).
, 300 MHz): δ 7.28-7.60 (m,
CH C), 4.10-
2
-
5
00 MHz): δ 4.21 (q, J ) 7.1 Hz, 2H, OCH
2
), 4.18 (q, J ) 7.1
), 2.67 (ABd, J AB
), 2.48 (ABd, J AB
19.5, J ) 9.4 Hz, 2H, 2 CHHCdO), 2.12 (ABd, J AB ) 19.5,
2
3
2
Hz, 2H, OCH
)
2
), 2.83 (br m, 2H, 2 CH
2
CHCH
Et)
2
3
14.1, J ) 8.1 Hz, 2H, 2 CHCHHC(CO
2
2
3
2 2
O
)
3
2 2
O
J ) 4.0 Hz, 2H, 2 CHHCdO), 2.00 (ABd, J AB ) 14.5, J ) 7.1
6 5
H
Hz, 2H, 2 CHCHHC(CO
CH CH ), 1.24 (t, J ) 7.1 Hz, 3H, CH
: C, 62.67; H, 7.51. Found: C, 62.42; H, 7.46.
Bicyclop en ta n on e 5: 1H NMR (CDCl
, 300 MHz): δ 7.71
d, J ) 8.1 Hz, 2H, 2 aromatic H), 7.35 (d, J ) 8.1 Hz, 2H, 2
aromatic H), 3.46 (dd, J ) 10.1, 7.4 Hz, 2H, 2 CHHCdO), 3.08
dd, J ) 10.7, 4.3 Hz, 2H, 2 CHHCdO), 2.88 (br m, 2H, 2
CH CHCH ), 2.45 (s, 3H, CH ), 2.43 (obscured dd, J ) 19.5,
.7 Hz, 2H, 2 NCHH), 2.01 (dd, J ) 19.5, 4.8 Hz, 2H, 2 NCHH).
2
Et)
2
), 1.26 (t, J ) 7.1 Hz, 3H,
6
H
5
2
2
2
3
2
CH ). Anal. Calcd for
3
2
C
14
H
20
O
5
2
2
3
CHHCHCH
2
CdO), 1.31 (t, J ) 7.4 Hz, 3H, CH
CH C).
En on e 26: H NMR (CDCl , 500 MHz): δ 7.27-7.43 (m,
5H, aromatic H), 3.93 (ABd, J AB ) 10.7, J ) 4.7 Hz, 1H,
HOCHHCHCH CdO), 3.85 (ABd, J AB ) 10.7, J ) 5.4 Hz,
3 2 2
CH O C), 1.23
(
(
t, J ) 7.4 Hz, 3H, CH
3
2 2
O
1
(
3
2
2
3
8
2
+
HOCHHCHCH CdO), 2.98-3.06 (m, 1H, HOCH CHCH Cd
MS [CI, m/z (rel intensity)]: 280.2 (M + 1, 100). Anal. Calcd
for C14 NS: C, 60.19; H, 6.13. Found: C, 60.03; H, 6.23.
Bicyclop en ta n on e 17: 1H NMR (CDCl
, 500 MHz): δ 4.20
q, J ) 7.1 Hz, 2H, CH CH C), 4.17 (q, J ) 7.1 Hz, 2H,
CH CH C), 2.74 (obscured m, 1H, CH
2
2
2
H
17
O
3
2
O), 2.69 (dd, J ) 18.1, 6.7 Hz, 1H, HOCH CHCHHCdO), 2.46
(dd, J ) 18.8, 2.0 Hz, 1H, HOCH
2
CHCHHCdO), 2.18 (s, 3H,
CHCH CdO). Anal.
2
O: C, 75.85; H, 6.85. Found: C,
3
CH
3
CdCC
6
H
5
), 1.60 (br s, 1H, HOCH
‚0.2 H
2
2
(
3
2 2
O
Calcd for C13
H
14
O
2
3
2
O
2
2
CHCH
2
CdO), 2.70
7
7
5.75; H, 6.59.
(
(
(
8
1
obscured dd, J ) 14.2, 8.0 Hz, 1H, CHHCHCHCH
3
CdO), 2.66
CdO), 2.44
Alk en e 27:56 1H NMR (CDCl
.0 Hz, 4H, (CH CH
C) × 2), 2.94 (s, 4H, (CCH
CH
) × 2), 1.24 (t, J ) 7.0 Hz, 6H,
C) × 2), 0.95 (t, J ) 7.4 Hz, 6H, (CCH CH ) × 2).
En on e 28: H NMR (CDCl , 300 MHz): δ 4.25 (q, J )
.4 Hz, 2H, CH CH C), 4.21 (q, J ) 7.4 Hz, 2H, CH CH C),
.23 (AB, J AB ) 19.5 Hz, 1H, CHHCdCCH CdO), 3.14 (AB,
AB ) 19.8 Hz, 1H, CHHCdCCH CdO), 2.81 (dd, J ) 12.8,
.4 Hz, 1H, CHHCHCHCH CdO), 2.60 (m, 1H, CH CHCH-
CdO), 2.09 (dq, J ) 2.7, 7.4 Hz, 1H, CH CHCHCH Cd
O), 1.72 (obscured s, 3H, CH CdCCH CdO), 1.70 (obscured
dd, J ) 12.8, 12.8 Hz, 1H, CHHCHCHCH CdO), 1.29 (t, J )
7.4 Hz, 3H, CH CH C), 1.26 (t, J ) 7.4 Hz, 3H, CH CH C),
.21 (d, J ) 7.4 Hz, 3H, CH CHCHCH CdO).
, 300 MHz): δ 3.71 (s, 6H,
, 300 MHz): δ 4.18 (q, J )
C) × 2), 2.03
3
obscured dd, J ) 13.6, 7.7 Hz, 1H, CHHCHCH
dd, J ) 19.1, 8.9 Hz, 1H, CH
2
3
2
O
2
2
2
CHCHHCdO), 2.32 (dddd, J )
CHCHCH CdO), 2.23 (dd, J )
CHCHHCdO), 2.16 (dd, J ) 14.2, 4.9
CdO), 2.02 (dq, J ) 7.4, 7.4 Hz, 1H,
CdO), 1.95 (dd, J ) 13.2, 9.9 Hz, 1H, CHHCH-
CdO), 1.26 (t, J ) 7.1 Hz, 3H, CH CH C), 1.24 (t, J )
CH C), 1.08 (d, J ) 7.1 Hz, 3H, CH
CdO). Anal. Calcd for C15 : C, 63.81; H, 7.85.
Found: C, 63.93; H, 7.87.
(
q, J ) 7.4 Hz, 4H, (CCH
2
3
.0, 7.4, 4.9, 2.8 Hz, 1H, CH
9.4, 3.1 Hz, 1H, CH
2
3
(CH CH
3
2
O
2
2
3
2
5
4
1
Hz, 1H, CHHCHCHCH
CH
CH
7.1 Hz, 3H, CH
CHCHCH
3
3
7
3
J
7
CH
3
2
O
2
3
2 2
O
2
CHCHCH
3
2 2
O
3
2
3
O
2
2
-
3
3
2
22 5
H O
3
2
3
3
2
3
Bicyclop en ta n on e 18: 1H NMR (CDCl
2
3
3
, 500 MHz): δ 7.33
meta
3
(dd, J ) 7.8, 7.1 Hz, 2H, aromatic H
), 7.25 (t, J ) 7.1 Hz,
H, aromatic Hpara), 7.14 (d, J ) 7.8 Hz, 2H, aromatic H
ortho
3
2
O
2
3
2 2
O
1
4
1
),
1
2
3
.21 (q, J ) 7.0 Hz, 4H, 2 CH
H, CH CHCHC
CHCHC
CHCHHCdO), 2.67 (dd, J ) 15.1, 6.8 Hz, 1H, CHHCHCH
O), 2.63 (dd, J ) 18.6, 7.8 Hz, 1H, CHHCHCHC CdO), 2.39
d, J ) 18.6 Hz, 1H, CHHCHCHC CdO), 2.32 (dd, J ) 14.6,
.4 Hz, 1H, CHHCHCH CdO), 2.06 (dd, J ) 13.2, 8.3 Hz, 1H,
CH CHCHHCdO), 1.26 (t, J ) 7.0 Hz, 3H, CH CH C), 1.25
CH C). Anal. Calcd for C20 : C,
3
CH
2
O
2
C), 3.26 (d, J ) 7.3 Hz,
Alk en e 29:57 H NMR (CDCl
1
3
2
3
2
6
H
5
2 2
CdO), 2.88-2.92 (m, 2H, CH CHCH Cd
CdO), 2.79 (dd, J ) 13.7, 6.8 Hz, 1H, CH
(OCH
3
) × 2), 2.45 (br s, 2H, CH
.7 Hz, 2H, CH CH CCH dCCH
), 1.63 (s, 3H, CCH
CCH
), 1.97 (br m, 2H, CH
), 1.57 (s, 3H, CCH
). IR (cm ): 2956, 1736, 1437, 1259.
3
dCCH
3
), 2.10 (t, J )
O, CH
2
6
H
5
2
-
6
2
2
3
2
CH
2
-
2
Cd
CCH
CCH
3
3
dCCH
3
3
dCCH
3
3
d
6
H
5
-
1
(
3
6 5
H
Alk en e 31:58 H NMR (CDCl
1
, 300 MHz): δ 4.17 (q, J )
C) × 2), 2.44 (br s, 2H, CH CCH
), 2.10 (t, J ) 7.3 Hz, 2H, CH CH CCH dCCH ), 1.98
br m, 2H, CH CH CCH dCCH ), 1.64 (s, 3H, CCH dCCH ),
.58 (s, 3H, CCH dCCH ), 1.23 (t, J ) 7.0 Hz, 6H, (CH
C) × 2).
En on e 32: 1H NMR (CDCl
CH CdCHCdO), 4.30 (q, J ) 7.3 Hz, 2H, CH
q, J ) 7.3 Hz, 2H, CH CH C), 2.84 (obscured dddd, J )
3
2
7
.0 Hz, 4H, (CH
3
CH
2
O
2
2
3
d
2
3
2 2
O
H O
24 5
CCH
(
1
3
2
2
3
3
(
6
t, J ) 7.0 Hz, 3H, CH
3
2
O
2
2
2
3
3
3
3
9.75; H, 7.02. Found: C, 69.55; H, 6.97.
3
3
3
-
-
Bicyclop en ta n on e 19: 1H NMR (CDCl
, 500 MHz): δ 7.71
3
2 2
CH O
ortho
(
d, J ) 8.0 Hz, 2H, aromatic H
), 7.34 (d, J ) 8.0 Hz, 2H,
meta
3
, 500 MHz): δ 5.89 (s, 1H, CH
CH
2
aromatic H
CH
), 3.48 (dd, J ) 10.1, 8.7 Hz, 1H, NCHHCH-
2
3
2
O
2
C), 4.20
2
CdO), 3.36 (dd, J ) 10.3, 6.0 Hz, 1H, NCHHCHCHCH
3
Cd
CdO),
CdO), 2.81
CHCH CdO),
N), 2.40 (dd, J ) 19.0, 8.7 Hz, 1H,
CHCHHCdO), 2.36 (dddd, J ) 7.3, 6.0, 3.9, 2.7 Hz,
H, NCH CHCHCH CdO), 2.20 (dd, J ) 19.3, 3.4 Hz, 1H,
CHCHHCdO), 1.87 (dq, J ) 7.3, 7.3 Hz, 1H, NCH
CdO), 1.04 (d, J ) 7.1 Hz, 3H, NCH CHCHCH Cd
(
3
2 2
O
O), 3.33 (dd, J ) 10.3, 2.7 Hz, 1H, NCHHCHCHCH
3
(
2
NCH
1
NCH
CHCHCH
3
.02 (dd, J ) 10.1, 6.7 Hz, 1H, NCHHCHCH
2
ddddd, J ) 8.7, 8.7, 6.7, 3.9, 3.4 Hz 1H, NCH
2
2
(55) Murimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J . Org.
Chem. 1997, 62, 3762.
56) Grigg, R.; Malone, J . F.; Mitchell, T. R. B.; Ramasubbu, A.;
Scott, R. M. J . Chem. Soc., Perkin Trans. 1 1984, 1745.
57) Ackermann, L.; F u¨ rstner, A.; Weskamp, T.; Kohl F.; Hermann,
3 6 4 2
.44 (s, 3H, CH C H SO
(
2
2
3
(
2
2
-
W. Tetrahedron Lett. 1999, 4787.
(58) Kirkland, T. A.; Grubbs, R. H. J . Org. Chem. 1997, 62, 7310.
3
2
3

1
246 J . Org. Chem., Vol. 67, No. 4, 2002
Krafft et al.
1
2.7, 6.4, 2.4, 2.4 Hz, 1H, CH
CHHCdCHCdO), 2.76 (obscured ddd, J
13.2, 5.4, 2.4 Hz, 1H, CHHCHCH CdO), 2.65 (obscured m,
H, CHHCH CdCHCdO), 2.63 (obscured dd, J ) 19.0, 6.4 Hz,
H, CH CHCHHCdO), 2.51 (ddd, J ) 14.2, 14.2, 5.4 Hz, 1H,
CHHCdCHCdO), 2.01 (dd, J ) 19.0, 2.4 Hz, 1H, CH
CHCHHCdO), 1.82 (ddd, J ) 13.7, 13.7, 4.9 Hz, 1H,
CHHCH CdCHCdO), 1.56 (dd, J ) 12.7, 12.7 Hz, 1H,
CHHCHCH CdO), 1.30 (t, J ) 7.3 Hz, 3H, CH CH C), 1.24
t, J ) 7.3 Hz, 3H, CH CH C). Anal. Calcd for C15 : C,
4.27; H, 7.19. Found: C, 64.02; H, 7.18.
B. Mon ocyclic Alk en e F or m a tion : Red u ctive Cycliza -
2
CHCH
2
CdO), 2.80 (obscured dm,
Typical experimental procedure for the silane-induced re-
J ) 14.2 Hz, 1H, CH
2
ductive cyclizations of enyne-Co
the reactions depicted in Tables 11-13: In a round-bottom
vessel equipped with a three-way stopper and a balloon of H
enyne-Co (CO) complex 1a (31 mg, 0.059 mmol) was pumped
briefly and purged three times with H . Et SiH (2.4 µL, 0.015
2 6
(CO) complexes. These are
)
1
1
2
2
2
,
2
2
6
CH
2
2
-
2
3
mmol) in toluene (1.3 mL) was then added, and the mixture
was heated at 60 °C for 2 h. Upon completion of the reaction,
the brown mixture was cooled to room temperature and then
treated with a solution of N-methylmorpholine N-oxide in
chloroform. Filtration of the mixture through a short pad of
coarse silica gel using a solution of 10% EtOAc in hexanes
provided a colorless solution. Subsequent removal of the
2
2
3
2 2
O
(
6
3
2
O
2
20 5
H O
tion of En yn es. 1. Rep r esen ta tive Exp er im en ta l P r oce-
d u r es. Typ ica l exp er im en ta l p r oced u r e for reactions
depicted in Table 8: In a round-bottom vessel equipped with a
2
solvent and purification by flash chromatography (SiO , 3%
EtOAc in hexanes) afforded 9 mg of the monocyclic alkenes
37 (62% yield, 3:1 ratio of endo to exo alkene isomers). A
similar general procedure was followed in the other reactions
where alternative sources of hydrides were used (Table 12).
three-way stopper and a balloon of H
24 mg, 0.086 mmol) and Co (CO) (31 mg, 0.091 mmol) was
pumped briefly and purged three times with H . A solution of
2
, a mixture of enyne 35
(
2
8
2
cyclohexylamine (31 µL, 0.27 mmol) in toluene (4.6 mL) was
then added, and the mixture was heated at 80 °C for 2.5 h.
Upon completion of the reaction, the brown mixture was cooled
to room temperature and treated with a solution of NMO in
chloroform until a clear solution was obtained. Filtration of
the mixture through a short pad of coarse silica gel using a
solution of 10% EtOAc in hexanes provided a colorless solution.
Subsequent removal of the solvent and purification by flash
chromatography (SiO
of enone 36 (70% yield) as a colorless oil. A similar general
procedure was followed in the other reactions where the
enyne-Co
tive cobalt carbonyl source, or DME as an alternative solvent.
The desired amount of cyclohexylamine was added as a
solution in the appropriate solvent, otherwise only the solvent
was added into the reaction mixture.
Typ ica l exp er im en ta l p r oced u r e for reactions depicted
in eq 5: In a round-bottom vessel equipped with a three-way
stopper and a balloon of H
mg, 0.093 mmol) was pumped briefly and purged three times
with H . It was then dissolved in CH Cl (1.9 mL), and a
solution of Me NO in CH Cl (0.47 mL, 0.094 mmol, 0.20 M)
was then added thrice at 1 h intervals at room temperature.
Additional quantities of Me NO in CH Cl (0.90 mL, 0.18
mmol) was added, and the mixture was stirred overnight.
Upon completion of the reaction, the mixture was filtered
through a short pad of coarse silica gel using a solution of 10%
EtOAc in hexanes. Subsequent removal of the solvent and
2. Alk en e 37:58 1H NMR (CDCl
7.0 Hz, 4H, (CH CH
CdCCH
3
, 300 MHz): δ 4.18 (q, J )
C) × 2), 2.92 (br s, 4H, (CCH C) × 2),
), 1.24 (t, J ) 7.0 Hz, 6H, (CH CH C)
3
2
O
2
2
1.59 (s, 6H, CH
× 2).
3
3
3
2 2
O
En yn e 39:59 1H NMR (CDCl
, 300 MHz): δ 7.26-7.38 (m,
3
10H, aromatic H), 5.77 (ddt, J ) 16.8, 9.4, 8.1 Hz, 1H,
CH CHdCH ), 5.08 (dm, J ) 16.1 Hz, 1H, CH CHdCHH), 5.04
(dm, J ) 8.1 Hz, 1H, CH CHdCHH), 4.49 (s, 4H, (C CH
× 2), 3.41 (AB, J AB ) 8.7 Hz, 1H, C CH OCHHC), 3.37 (AB,
AB ) 8.7 Hz, 1H, C CH OCHHC), 2.28 (d, J ) 2.7 Hz, 2H,
CH CCH), 2.24 (d, J ) 7.4 Hz, 2H, CH CHdCH ), 1.94 (t, J )
2
2
2
2
6
H
5
2
)
2
, 20% EtOAc in hexanes) afforded 19 mg
6
H
5
2
J
6
H
5
2
2
2
2
2
(CO)
6
complex or Co
4
(CO)12 was used as an alterna-
2
2.7 Hz, 1H, CH CCH).
Alk en e 41:57 H NMR (CDCl
, 300 MHz): δ 7.72 (d, J )
1
3
ortho
7.8 Hz, 2H, aromatic H
), 3.97 (s, 4H, (NCH
1.54 (s, 6H, CH CdCCH
), 7.31 (d, J ) 8.3 Hz, 2H, aromatic
meta
H
2
C) .) × 2), 2.42 (s, 3H, CH
3 6 4 2
C H SO N),
3
3
1
En on e 42: H NMR (CDCl
3
, 500 MHz): δ 7.27-7.36 (m,
CdCHCdO), 4.55 (s, 2H,
O), 3.53 (AB, J AB ) 8.8 Hz,
2
OCHHC), 3.51 (AB, J AB ) 8.8 Hz, 1H, C CH -
10H, aromatic H, 5.83 (s, 1H, CH
2
2
, enyne-Co
2
(CO)
6
complex 1a (49
C
6
H
1H, C
5
CH
2
5
O), 4.49 (s, 2H, C
CH
6 5 2
H CH
6
H
2
6
H
5
2
2
2
OCHHC), 3.37 (AB, J AB ) 8.8 Hz, 1H, AB, J AB ) 8.8 Hz, 1H,
CH OCHHC), 3.31 (AB, J AB ) 8.8 Hz, 1H, AB, J AB ) 8.8
Hz, 1H, C CH OCHHC), 3.09-3.14 (m, 1H, CH CHCH Cd
O), 2.59 (obscured dd, J ) 17.6, 6.3 Hz, 1H, CH CHCHHCd
O), 2.58 (obscured s, 2H, CH CdCHCdO), 2.17 (dd, J )
12.7, 8.8 Hz, 1H, CHHCHCH CdO), 2.03 (dd, J ) 17.6, 2.9
Hz, 1H, CH CHCHHCdO), 1.12 (dd, J ) 12.7, 12.7 Hz, 1H,
CHHCHCH CdO). Anal. Calcd for C24 : C, 79.53; H, 7.23.
3
2
2
C
6
H
5
2
6
H
5
2
2
2
3
2
2
2
2
2
2
2
26 3
H O
purification by flash chromatography (SiO
hexanes) afforded 20 mg of enone 3 (80% yield) as a colorless
oil. A similar general procedure was followed in the reactions
2
, 20% EtOAc in
Found: C, 79.46; H, 7.33.
1
Alk en e 43: H NMR (CDCl
3
, 300 MHz): δ 7.27-7.39 (m,
CH
O) × 2), 3.41 (s, 4H,
C) × 2), 2.17 (s, 4H, (CCH C) × 2), 1.55 (d, J
) 1.3 Hz, 6H, CH CdCCH ). Anal. Calcd for C23 ‚0.10
O: C, 81.67; H, 8.34. Found: C, 81.66; H, 8.30.
10H, aromatic H), 4.52 (s, 4H, C
(C CH OCH
6
H
5
2
where NMO (as a solution in CH
alternative oxidant. In the reaction using Et
was added into the reaction mixture as a solution in CH
2
Cl
2
) was used as an
SiH, the silane
Cl
6
H
5
2
2
2
3
3
3
28 2
H O
2
2
H
2
prior to the incremental addition of NMO (1 × 5 equiv) at 1 h
intervals at room temperature.
Typical experimental procedure for reactions depicted in
Table 9: In a round-bottom vessel equipped with a three-way
Ack n ow led gm en t . Support for this work was
provided by the National Science Foundation and
donors to the Krafft Research Fund. We acknowledge
Professor Neil Schore (UC, Davis) and Professor Carl
Hoff (U. Miami, FL) for helpful discussions.
stopper and a balloon of H
mg, 0.12 mmol) was pumped briefly and purged three times
with H . Toluene (2.4 mL) was then added, and the mixture
2
, enyne-Co
2 6
(CO) complex 1a (64
2
was heated at 60 °C for 5 h. Upon completion of the reaction,
the brown mixture was cooled to room temperature and then
treated with a solution of N-methylmorpholine N-oxide in
chloroform. Filtration of the mixture through a short pad of
coarse silica gel using a solution of 10% EtOAc in hexanes
provided a colorless solution. Subsequent removal of the
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra of compounds 21 and 22 and IR and 13C NMR spectral
data for compounds 2, 5, 8, 16-19, 21, 26, 32, 42, 43. This
material is available free of charge via the Internet at
http://pubs.acs.org.
solvent and purification by flash chromatography (SiO
0%, and then 50% EtOAc in hexanes) afforded 15 mg of the
2
, 3%,
2
monocyclic alkenes 37 (52% yield, 1:1 ratio of endo to exo
alkene isomers) and 5 mg of enone 3 (16% yield). A similar
general procedure was used for the reactions carried out with
different solvents (Table 10).
J O016118V
(59) Urabe, H.; Hata, T.; Sato, F. Tetrahedron Lett. 1995, 36, 4261.